Process for the preparation of one or more c-glycoside derivatives comprising a catalytic reduction stage

Abstract

The present invention relates to a process for the preparation of one or more C-glycoside derivatives corresponding to the formula (I), preferably corresponding to the formula (I'), and to their optical isomers, geometrical isomers and / or solvates, such as the hydrates, comprising at least one purification stage carried out in an aqueous medium. The invention also relates to a process for the preparation of one or more C-glycoside derivatives corresponding to the formula (I'B), comprising a stage of reduction, carried out in an aqueous medium, of at least one compound of formula (I), preferably of formula (I').

Description

[0001] DESCRIPTION

[0002] TITLE: Process for the preparation of one or more C-glycoside derivatives comprising a catalytic reduction stage

[0003] The present invention relates to a process for the preparation of one or more C-glycoside derivatives corresponding to the formula (I), as described below, preferably corresponding to the formula (f) or (I"), and to their optical isomers, geometrical isomers and / or solvates, such as the hydrates, comprising at least one purification stage carried out in an aqueous reaction medium.

[0004] The invention also relates to a process for the purification of at least one aqueous reaction medium including at least one C-glycoside derivative corresponding to the formula (I) and at least one impurity of formula (IV), as described below.

[0005] Processes for the synthesis of water-soluble organic active agents having advantageous cosmetic properties can result in the formation of impurities, which are in an ionic form, which generally prove to be tedious to minimise, indeed even to remove, without impacting to a greater or lesser extent the yield of the final cosmetic active compound.

[0006] Moreover, such impurities, when they are present with the final cosmetic active compound, can generate a colour, a modification in texture or an odour which is not desired in the cosmetic compositions employing said active agent. Thus, such impurities can be the source of an unpleasant and marked odour, for example a pungent and strongly vinegary odour, liable to manifest itself, even after several purification operations have been carried out, and to prove to be inconvenient and persistent even after formulation for consumers, all the more so since the current trend is to use fewer and fewer fragrances in cosmetic products to mask or neutralise odours of this type.

[0007] Such impurities can also give rise to problems of compatibility with other additives optionally present in the final cosmetic formulations.

[0008] Such impurities can also be salts of acids or of bases which will have an effect on the pH in an aqueous medium. This effect is all the more of a nuisance as the cosmetic active agent is isolated in the form of a concentrated aqueous solution.

[0009] In addition, the presence of such impurities, in particular of inorganic and / or organic salts, can induce a considerable increase in the viscosity of the aqueous reaction medium comprising the cosmetic active agent(s), thus making it difficult, in certain cases, to obtain concentrated solutions of cosmetic active agents intended for the formulation.

[0010] By way of example, C-glycoside derivatives are water-soluble organic compounds, the properties of which are generally advantageous in the field of cosmetics, in particular in care compositions, in order to be used to stimulate the synthesis of glycosaminoglycans present in the dermis and in particular to provide density and firmness to the skin (see, for example, the scientific paper entitled: Synthesis of Pro-Xylane™: A New Biologically Active C-glycoside in Aqueous Media, M. Dalko-Csiba el al., Bioorganic & Medicinal Chemistry Letters, 19 (2009), 845-849).

[0011] C-glycoside derivatives, such as xylose C-glycoside derivatives, are generally synthesised by means of a reaction, known as the Lubineau reaction (Rodrigues, F., Canac, Y. and Lubineau, A., A Convenient, One-Step, Synthesis of P-Glycosidic Ketones in Aqueous Media, Chemical Communications, 2000 (20), 2049-2050), from a monosaccharide or a polysaccharide which is unprotected, for example D-xylose, and a P-dicarbonyl compound, for example acetyl acetone, in an aqueous medium in the presence of alkaline agent(s).

[0012] The Lubineau reaction is carried out with at least one alkaline agent, such as sodium bicarbonate or sodium hydroxide, present in an equimolar amount or in excess with respect to the monosaccharide or polysaccharide, preferably in excess, for a reaction time capable of varying from 5 minutes to 20 hours depending on the nature of the alkaline agent and / or on the reaction parameters, such as the concentration and / or the temperature.

[0013] However, such a synthesis reaction exhibits in particular the major pitfail of resulting in the formation of impurities, being in particular in the form of salts, for example in the form of an organic salt, such as sodium acetate, the residual amounts of which can prove to be significant and difficult to reduce, even by carrying out several conventional purification and / or washing operations.

[0014] On conclusion of this reaction, the aqueous reaction medium can be neutralised with at least one, in particular mineral, acidifying agent, for example hydrochloric acid, in order to convert the organic acid salt into an organic acid, in particular by converting sodium acetate into acetic acid, in order to subsequently reduce the amounts of organic acid to commercially acceptable contents.

[0015] However, the neutralisation of the reaction medium with at least one mineral acidifying agent, such as hydrochloric acid, also results in the formation of salts, in particular of sodium chloride, which can be removed by precipitation by virtue of the addition of water-miscible solvents, such as alcohols, in particular isobutanol or ethanol.

[0016] It is known from the prior art to add, at the end of the reaction, a water- immiscible solvent in order to wash the aqueous reaction medium and then to pass the aqueous medium over a preconditioned acidic resin before concentrating in the presence of alcohol. To do this, successive distillation operations, in particular to remove the water, then the addition of alcohol, can cause crystallisation of salts, followed by optional washing operation(s), carried out with several cycles of addition of water, to reduce the amount of salts to acceptable contents within commercial solutions intended to be used in the cosmetic field.

[0017] On conclusion of these various purification operations, the C-glycoside derivatives obtained can be pure and solvent-free and are subsequently subjected, in certain cases, to a hydrogenation reaction targeted at reducing the ketone function of the C-glycoside derivative resulting from the P-dicarbonyl derivative to give a hydroxyl function.

[0018] In particular, xylose C-glycoside derivatives, such as C-P-D-xylopyranoside- n-propane-2-one, can subsequently be subjected to a reduction reaction to result in C- P-D-xylopyranoside-2-hydroxypropane.

[0019] However, such purification operations, including those carried out several times in succession, have not made it possible to satisfactorily reduce the impurities generated during the process for the preparation of the C-glycoside derivatives, in particular on the industrial scale.

[0020] This is because such purification operations exhibit the disadvantage of having to be carried out several times in order to sufficiently reduce the contents of impurities satisfactorily and, when the impurities are malodorous, to minimise the odours generated by certain impurities, such as acetic acid, which are disagreeable and to be avoided for cosmetic use. In addition, the formation of sodium chloride during the neutralisation stage requires the implementation of operations of washing, carried out with addition of water or of organic solvents, in particular of alcohols, and optionally of distillation in order to be suitably removed.

[0021] Such purification operations, a fortiori repeated, thus exhibit the disadvantage of reducing the yield, of generating additional organic effluents, of increasing the number of stages and / or of being tedious to carry out industrially both to reduce the content of organic acid, in particular of acetic acid, and to reduce the content of salts, for example of sodium chloride, in the final cosmetic active agent intended for the formulation of cosmetic products.

[0022] Moreover, the use of organic solvents, in particular (non-)polar aprotic organic solvents, during washing operations often has the disadvantage of not sufficiently reducing the impurities and of leading to the implementation of additional operations of washing or neutralisation, indeed even of purification by chromatography and / or crystallisation, likely to further harm the yield. Such additional operations are tedious to carry out on the industrial scale. In addition, residual contents of organic solvent(s) can persist in the solutions of cosmetic active agents employed in the final cosmetic formulations, which is not desirable.

[0023] The result of this is that the purification operations conventionally employed in processes for the preparation of C-glycoside derivatives do not result in a yield and in a degree of purity which are sufficiently satisfactory, in particular for manufacture on the industrial scale, reproducible and robust, for use in the field of cosmetics.

[0024] In view of the foregoing, there thus exists a real need to employ a new process for the preparation of C-glycoside derivatives which does not exhibit the abovementioned disadvantages, resulting in particular in an improved degree of purity and a higher yield and the implementation of which is more optimised, specifically industrially, in terms of quality of the product on the industrial scale, of number of purification stages, of implementation and / or of organic effluents generated.

[0025] In other words, one of the aims of the present invention is in particular to provide a process for the preparation of one or more C-glycoside derivatives, during which the impurities are minimised in order to be able to be efficiently carried out on the industrial scale for cosmetic applications.

[0026] In particular, one of the aims of the present invention is to provide a process for the preparation of one or more C-glycoside derivatives during which the impurities, including those capable of generating an unpleasant or disagreeable odour, for example a pungent and strongly vinegary odour, in particular resulting from the synthesis stage, are minimised in order to be able to be efficiently carried out on the industrial scale for cosmetic applications.

[0027] A subject-matter of the present invention is thus in particular a process for the preparation of at least one compound of following formula (I): in which formula (I):

[0028] - SA' represents a monosaccharide group or a polysaccharide group comprising up to 20 sugar units, in particular up to 6 sugar units, preferably a monosaccharide, di saccharide or tri saccharide, more preferentially monosaccharide, in pyranose and / or furanose form and of L and / or D series, said monosaccharide group or polysaccharide group being substituted by at least one free hydroxyl group, and optionally at least one amine group which is optionally protected, in particular by an acetyl group R'-C(Y)- with R' representing a hydrogen atom or a (Ci-Ce)alkyl group, such as methyl, and Y representing O or S, preferably O,

[0029] - the bond between SA' and CH2-X is a bond of C-anomeric nature,

[0030] - X represents a divalent radical -C(O)- or -CH(OR)-,

[0031] - R represents a hydrogen atom, a C1-C10, preferably C1-C4, alkyl group, such as methyl, or a (Ci-C4)alkylcarbonyl group, such as acetyl, preferably a hydrogen atom,

[0032] - Ri represents a saturated or unsaturated, linear or branched, cyclic or acyclic, preferably acyclic, C1-C10, preferably C1-C4, more preferentially saturated, in particular Ci, hydrocarbon chain, and also one of its optical isomers, geometrical isomers, and / or one of its solvates, such as the hydrates, said process comprising:

[0033] - at least one reaction stage (i) taking place according to the following synthesis

[0034] (ID 01) W OT) in which synthetic pathway (A):

[0035] ■ Ri and R2 are identical or different, with R2 having the same meaning as Ri in the formula (I),

[0036] ■ SA' has the same meaning as in the formula (I),

[0037] ■ D+is an organic or inorganic cation resulting from the alkaline agent; preferably, D+is an inorganic cation, said reaction stage (i) being carried out in an aqueous media in the presence: ■ of at least one compound of formula (II),

[0038] ■ of at least one compound of formula (III), and

[0039] ■ of at least one alkaline agent in an equimolar amount or in excess, with respect to the compound of formula (II), preferably in excess, to result in the formation of at least one compound of formula (IA) and of at least one compound of formula (IV),

[0040] - optionally, at least one stage of reaction (ii) of at least said compound of formula (IA) in a preferably aqueous medium, to result in the formation of at least one compound corresponding to the following formula (IB):

[0041] (IB) in which formula (IB):

[0042] - SA', Ri and R have the same meanings as in the formula (I),

[0043] - at least one purification (P) of the reaction medium including at least said compound of formula (IV), carried out in an aqueous medium, comprising:

[0044] ■ at least one treatment stage (Pl) carried out with at least one cationic ion-exchange resin in order to convert at least said compound of formula (IV) into a compound of formula (IV) according to the following scheme: said treatment stage (Pl) being carried out at a pH strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), if several are present,

[0045] ■ at least one stage of separation (P2) of at least said compound of formula (IV) from the reaction medium.

[0046] The expression “bond between SA' and CH2-X" which is a bond of C- anomeric nature is understood to mean that the part of the sugar moiety SA' is connected to the remainder of the molecule via the methylene group -CH2- by a carbon- carbon C-C bond (i.e., carbon of the sugar SA'-carbon of the methylene -CH2-) and not by an oxygen-carbon O-C bond (i.e., not by an oxygen of the sugar SA'-carbon of the methylene -CH2- bond).

[0047] Within the meaning of the present invention, SA' comprises a monosaccharide or polysaccharide SA group comprising up to 20 sugar units, as defined above, SA being substituted by at least one free hydroxyl group.

[0048] In other words, SA' has the same meaning as SA and comprises at least one free hydroxyl group (-OH).

[0049] Within the meaning of the present invention, a compound of formula (IA) is a compound of formula (I) in which X corresponds to a divalent radical -C(O)-.

[0050] Within the meaning of the present invention, a compound of formula (IB) is a compound of formula (I) in which X corresponds to a divalent radical -CH(OR)- with R as defined above; preferably, R represents a hydrogen atom.

[0051] In other words, the invention relates to a process for the preparation of one or more C-glycoside derivatives of formula (I), as described above, comprising at least one purification (P), carried out in an aqueous reaction medium, intended to minimise at least significantly the contents of ionic impurities of formula (IV) resulting from the synthesis stage (i).

[0052] Thus, the purification stage (P) has the advantage of being flexible to carry out during the preparation of at least one compound of formula (I).

[0053] This is because the purification stage (P) can be carried out at least once between the reaction stage (i) and the reaction stage (ii) and / or after at least one reaction stage (ii).

[0054] According to one embodiment, the purification stage (P) is carried out at least once on conclusion of the reaction stage(s) (i).

[0055] According to another embodiment, the purification stage (P) is carried out at least once on conclusion of the reaction stage(s) (ii).

[0056] According to a particular embodiment, the purification stage (P) is carried out at least once on conclusion of the stage(s) (i) and the process of the invention does not comprise a stage (ii).

[0057] According to another embodiment, the process of the invention comprises at least one stage (i), preferably one stage (i), and at least one stage (ii), preferably one stage (ii), and the purification stage (P) is carried out at least once on conclusion of at least one stage (i) without being carried out on conclusion of the stage(s) (ii). According to yet another embodiment, the process of the invention comprises at least one stage (i), preferably one stage (i), and at least one stage (ii), preferably one stage (ii), and the purification stage (P) is carried out at least once on conclusion of at least one stage (ii) without being carried out on conclusion of the stage(s) (i).

[0058] According to another embodiment, the process of the invention comprises at least one stage (i), preferably one stage (i), and at least one stage (ii), preferably one stage (ii), and the purification stage (P) is carried out at least once on conclusion of at least one stage (i) and at least once on conclusion of at least one stage (ii).

[0059] According to a preferred embodiment, the process of the invention comprises one stage (i) and one stage (ii) and the purification stage (P) is carried out at least once on conclusion of stage (i) without being carried out on conclusion of the stage(s) (ii).

[0060] The purification (P) is thus carried out in an aqueous reaction medium, that is to say in a reaction medium devoid of any organic solvent as described below.

[0061] Thus, the purification (P) according to the invention is devoid of any washing operation carried out with at least one organic solvent as described below.

[0062] The process according to the invention thus makes it possible to achieve the objectives as described above, that is to say that it results in one or more compounds of formula (I), having a high degree of purity with a satisfactory yield while exhibiting an optimised implementation industrially, in particular a robust and reproducible one, especially compared with the processes conventionally employed in the prior art.

[0063] In particular, the process according to the invention exhibits the advantage of minimising the impurities, including those usually giving rise to a marked and unpleasant odour, such as a pungent and strongly vinegary odour, which are particularly difficult to remove in the processes conventionally employed in the prior art.

[0064] More particularly, the treatment stage (Pl) is a neutralisation stage making it possible at least to significantly reduce the contents of salts formed during the reaction stage (i), that is to say the contents of the compound of formula (IV).

[0065] In other words, the treatment stage (Pl) makes it possible to significantly convert at least the compound of formula (IV) into a compound of formula (IV) and then the separation stage (P2) makes it possible to more easily reduce the contents of compound of formula (IV) without having to involve an organic solvent.

[0066] Thus, the process according to the invention, in particular the purification stage (P), exhibits in particular the advantage of not using an organic solvent to reduce the content of impurities resulting from the reaction stage (i), which greatly improves its environmental footprint while being easy to carry out industrially.

[0067] The process according to the invention then advantageously makes it possible to reduce the amounts of fragrances to be used to mask or neutralise the odours liable to be disagreeable during the preparation of a cosmetic formulation employing at least one compound of formula (I).

[0068] The process according to the invention also makes it possible to reduce the organic effluents at the reactor outlet and to limit the numerous washing operations conventionally carried out in the processes described in the prior art.

[0069] The process according to the invention exhibits in particular an implementation which is easier to optimise industrially than the conventional processes of the prior art, in particular those involving a successive implementation of several operations to reduce the impurities as much as possible, which makes it possible to process the synthesis reaction and the purification in one and the same reactor having a suitable format.

[0070] The process according to the invention makes it possible to dispense with the implementation of additional purification stages carried out by chromatography and / or crystallisation, which are not suitable industrially and / or which are likely to harm the yield.

[0071] The process according to the invention thus makes it possible to achieve a saving in the number of purification stages to be carried out on conclusion of the synthesis reaction (i) and / or (ii) in order to reduce the content of impurities of the compound (I).

[0072] Moreover, when the process according to the invention employs a reduction stage (ii), carrying out at least one purification stage (P) or (Pl) on conclusion of stage (i) prior to (ii) makes it much easier to obtain compounds of formula (I) with X = - CH(OR)- with a very good yield and a very good purity.

[0073] The process according to the invention also exhibits the advantage of easily controlling target levels of impurities, which makes it possible to obtain several grades of a compound of formula (I), depending on the desired content of impurities.

[0074] The process according to the invention thus makes it possible to more easily control the contents of impurities.

[0075] Another subject-matter of the invention is a process for the purification of an aqueous medium including at least one compound corresponding to the formula (I), as defined above, and at least one compound of formula (IV), as defined above, comprising:

[0076] ■ at least one treatment stage (Pl) carried out with at least one cationic ionexchange resin in order to convert at least said compound of formula (IV) into a compound of formula (IV) according to the following scheme: said treatment stage (Pl) being carried out at a pH strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), if several are present, and

[0077] ■ at least one stage of separation (P2) of at least said compound of formula (IV) from the reaction medium,

[0078] ■ at least one stage of reduction (iil) by catalytic hydrogenation carried out in the presence of at least one metal catalyst.

[0079] Other subject-matters, characteristics, aspects and advantages of the invention will become even more clearly apparent on reading the description and the example which follow.

[0080] In that which will follow and unless otherwise indicated, the limits of a range of values are included in this range, in particular in the expressions “of between” and “ranging from ... to ...”.

[0081] Moreover, the expression “at least one” used in the present description is equivalent to the expression “one or more”.

[0082] In addition, the expression "at least" used in the present description is equivalent to the expression "greater than or equal to". Finally, in a way known per se, the term "Cn" or "Cn" compound or group denotes a compound or a group containing, in its chemical structure, "n" carbon atoms.

[0083] Within the meaning of the present invention, the terms "purification (P)" and "purification stage (P)" are used without distinction.

[0084] Within the meaning of the present invention, the terms “alkaline agent” and

[0085] “hasifying agent” are used without distinction. The basifying agent(s) can be inorganic alkaline agents, preferably chosen from the group consisting of alkali metal hydroxides and alkaline earth metal hydroxides, such as lithium hydroxide, sodium hydroxide or potassium hydroxide, alkali metal and alkaline earth metal (bi)carbonates, such as sodium or potassium (bi)carbonates, and their mixtures.

[0086] The basifying agent(s) can be organic alkaline agents, preferably chosen from the group consisting of mono(Ci-C6)(hydroxy)alkylamines, di(Ci- C6)(hydroxy)alkylamines, tri(Ci-C6)(hydroxy)alkylamines (preferably tri(Ci- C6)(hydroxy)alkylamines), saturated or unsaturated cyclic amines which are aromatic, such as pyridine, or non-aromatic, optionally substituted by one or more (Ci-C4)alkyl groups, such as tetrahydropyridines optionally substituted by one or more (Ci-C4)alkyl groups, piperidines optionally substituted by one or more (Ci-C4)alkyl groups or piperazines optionally substituted by one or more (Ci-C4)alkyl groups. Preferably, the organic alkaline agents are organic amines, in particular tertiary amines, such as tri(Ci- C6)alkylamines.

[0087] Preferably, the basifying agents are chosen from the group constituted of alkali metal and alkaline earth metal hydroxides, in particular sodium hydroxide, alkali metal and alkaline earth metal (bi)carbonates, in particular sodium or potassium (bi)carbonates, and organic amines, preferably tertiary amines, such as triethylamine or diisopropylethylamine.

[0088] Preferably, the basifying agents are mineral.

[0089] More preferentially, the basifying agents are mineral and are chosen from the group consisting of alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal (bi)carbonates, and their mixtures, in particular alkali metal and alkaline earth metal hydroxides, in particular sodium hydroxide.

[0090] The acidifying agents capable of being used in the process according to the invention are any acidification means known to a person skilled in the art, such as bipolar electrodialysis or the addition of mineral acidifying agents, in particular of mineral acid type, such as sulfuric acid, phosphoric acid, sulfonic acid or phosphonic acid, the H+Hal' acids with Hal representing a halogen atom chosen from the group constituted of chlorine, bromine and iodine, preferably the H+Hal' acids with Hal preferably representing a chlorine atom; preferably by addition of mineral acidifying agents, in particular of the mineral acid type, such as sulfuric acid, phosphoric acid, sulfonic acid or phosphonic acid, the H+Hal' acids with Hal representing a halogen atom chosen from the group consisting of chlorine, bromine and iodine, preferably the H+Hal' acids with Hal preferably representing a chlorine atom.

[0091] More preferentially, the acidifying agent is hydrochloric acid.

[0092] Process for the preparation of at least one compound of formula (I)

[0093] As indicated above, the method according to the invention comprises:

[0094] - at least one reaction stage (i) taking place in an aqueous medium and according to the reaction scheme (A), as described above, in the presence:

[0095] ■ of at least one compound of formula (III), preferably in an equimolar amount or in excess with respect to the compound of formula (II), preferably in excess, and

[0096] ■ of at least one alkaline agent, preferably at least one mineral alkaline agent, in an equimolar amount or in excess, preferably in excess, with respect to the compound of formula (II), to result in the formation of at least one compound of formula (IA) (i.e. a compound corresponding to the formula (I) in which X corresponds to a divalent radical -CO-, and of at least one compound of formula (IV);

[0097] - optionally at least one reaction stage (ii) resulting in the formation of at least one compound of formula (IB) (i.e. a compound corresponding to the formula (I) in which X corresponds to a divalent radical -CH(OR)- with R preferably representing a hydrogen atom),

[0098] - at least one purification (P) of the reaction medium comprising at least the compound of formula (IV), carried out in an aqueous medium, comprising:

[0099] ■ at least one treatment stage (Pl) carried out with at least one cationic ion-exchange resin in order to convert at least said compound of formula (IV) into a compound of formula (IV) according to the following scheme: said treatment stage (Pl) being carried out at a pH value strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), if several are present,

[0100] ■ at least one stage of separation (P2) of at least said compound of formula (IV) from the reaction medium.

[0101] Reaction stage (i)

[0102] Advantageously, the reaction stage(s) (i) are carried out in an aqueous medium, in the presence:

[0103] ■ of at least one compound of formula (II),

[0104] ■ of at least one compound of formula (III),

[0105] ■ preferably, the compound(s) of formula (III) / compound(s) of formula (II) molar ratio is greater than or equal to 1, preferably of between 1 and 5, more preferentially between 1 and 4, more particularly still between 1 and 3, better still between 1 and 2, in particular ranging from 1 to 1.5; according to a particular embodiment, the compound(s) of formula (III) / compound(s) of formula (II) molar ratio is greater than 1;

[0106] ■ of at least one alkaline agent,

[0107] ■ preferably at least one alkaline agent as described above which is preferentially mineral, more preferentially chosen from the group consisting of alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal (bi)carbonates, and their mixtures; in particular alkali metal and alkaline earth metal hydroxides, such as sodium hydroxide,

[0108] ■ the alkaline agent being in an equimolar amount or in excess,

[0109] ■ preferably, the alkaline agent(s) / compound(s) of formula (II) molar ratio is greater than or equal to 1, preferably of between 1 and 5, more preferentially between 1 and 4, more particularly still between 1 and 3, better still between 1 and 2; according to a particular embodiment, the alkaline agent / compound of formula (II) molar ratio is greater than 1,

[0110] ■ preferably, the reaction stage (i) takes place:

[0111] ■ at a temperature ranging from 20°C to 80°C, preferably at a temperature ranging from 20°C to 70°C, more preferentially at a temperature ranging from 30°C to 70°C, better still from 30°C to 60°C, even better still at a temperature ranging from 35°C to 45°C,

[0112] ■ preferably, the duration of the reaction varies:

[0113] ■ from 10 minutes to 10 hours, preferably from 20 minutes to 5 hours, more preferentially from 30 minutes to 4 hours, more preferentially still from 45 minutes to 3 hours.

[0114] ■ preferably, the reaction (i) is carried out at atmospheric pressure.

[0115] Preferably, the reaction stage(s) (i) are carried out in an aqueous medium and successively comprise:

[0116] ■ preferably, the addition of at least one compound of formula (II) to an aqueous medium, in particular at a temperature varying from 20°C to 80°C,

[0117] ■ preferably, the addition of at least one compound of formula (III) to the aqueous medium comprising at least one compound of formula (II),

[0118] ■ optionally, the temperature is advantageously reduced by at least 5°C, in particular by at least 10°C, preferably by at least 20°C, before addition of at least one alkaline agent,

[0119] ■ preferably, the addition of at least one alkaline agent which is preferably mineral, in an equimolar amount with respect to the compound of formula (II) or in excess, preferably in excess, as described above, while maintaining the temperature preferentially less than or equal to 60°C, better still less than or equal to 50°C, even better still less than or equal to 45°C,

[0120] ■ preferably, the reaction medium comprising at least one compound of formula (II), at least one compound of formula (III) and at least one alkaline agent is maintained at the temperature of end of addition of at least one alkaline agent and / or heated to the reaction temperature as described above,

[0121] ■ optionally, on conclusion of the reaction (i), the reaction medium can be cooled by at least 5°C, preferably by at least 10°C, more preferentially by at least 15°C.

[0122] Preferably, on conclusion of the reaction stage(s) (i), the pH can be adjusted to a value of less than or equal to 8.5 and of greater than or equal to 2.5, preferably is adjusted within a range extending from 2.5 to 8.5. The pH can be adjusted by any acidification means known to a person skilled in the art, such as the use of at least one acidic resin and / or by addition of at least one acidifying agent as described above which is preferably mineral, more preferentially chosen from the group constituted of the mineral acids as described above.

[0123] According to a particular embodiment, the pH is adjusted by at least one acidic resin and optionally by addition of at least one acidifying agent as described above which is preferably mineral, more preferentially chosen from the group constituted of the mineral acids as described above.

[0124] According to a preferred embodiment, the process according to the invention comprises a stage (i).

[0125] Purification stage (P)

[0126] In accordance with the present invention, the purification stage (P) is carried out on an aqueous reaction medium comprising at least one impurity of formula (IV).

[0127] The purification stage (P) can thus be carried out one or more times on an aqueous reaction medium comprising at least one impurity of formula (IV).

[0128] According to one embodiment, the purification stage (Pl) is carried out one or more times and the purification stage (P2) is carried out at least once on conclusion of at least one stage (Pl).

[0129] The purification (P) can thus be carried out on an aqueous reaction medium resulting from the reaction stage (i) and / or on an aqueous reaction medium resulting from at least one reaction stage (ii).

[0130] In other words, the purification(s) (P) can be carried out at least once between a reaction stage (i) and at least one reaction stage (ii), and / or at least once after at least one reaction stage (ii), for example after one and / or two reaction stages (ii).

[0131] According to one embodiment, the purification stage (P) is carried out at least once on conclusion of the reaction stage(s) (i).

[0132] According to another embodiment, the purification stage (P) is carried out at least once on conclusion of the reaction stage(s) (ii).

[0133] According to a particular embodiment, the purification stage (P) is carried out at least once on conclusion of the stage(s) (i) and the process of the invention does not comprise a stage (ii).

[0134] According to another embodiment, the process of the invention comprises at least one stage (i), preferably one stage (i), and at least one stage (ii), preferably one stage (ii), and the purification stage (P) is carried out at least once on conclusion of at least one stage (i) without being carried out on conclusion of the stage(s) (ii).

[0135] According to yet another embodiment, the process of the invention comprises at least one stage (i), preferably one stage (i), and at least one stage (ii), preferably one stage (ii), and the purification stage (P) is carried out at least once on conclusion of at least one stage (ii) without being carried out on conclusion of the stage(s) (i).

[0136] According to another embodiment, the process of the invention comprises at least one stage (i), preferably one stage (i), and at least one stage (ii), preferably one stage (ii), and the purification stage (P) is carried out at least once on conclusion of at least one stage (i) and at least once on conclusion of at least one stage (ii).

[0137] According to a preferred embodiment, the process of the invention comprises one stage (i) and one stage (ii) and the purification stage (P) is carried out at least once on conclusion of stage (i) without being carried out on conclusion of the stage(s) (ii).

[0138] According to one embodiment, the purification stage (Pl) is carried out at least once on conclusion of the reaction stage(s) (i).

[0139] According to another embodiment, the purification stage (P2) is carried out at least once on conclusion of the reaction stage(s) (ii).

[0140] According to another embodiment, the process of the invention comprises at least one stage (i), preferably one stage (i), and at least one stage (ii), preferably one stage (ii), and a purification stage (Pl) is carried out at least once on conclusion of at least one stage (i) and a purification stage (P2) is carried out at least once on conclusion of at least one stage (ii).

[0141] Preferably, the purification (P) is carried out at least once between the reaction stage (i) and at least one reaction stage (ii).

[0142] In other words, when at least one stage (ii) exists, the purification stage (P) can be carried out at least before and / or at least after the reaction stage(s) (ii), preferably at least before the reaction stage(s) (ii).

[0143] Preferably, the purification (P) is carried out at least once on conclusion of the reaction stage (i).

[0144] When several stages (i) are carried out in the process, at least one purification (P) can be carried out on conclusion of each of the stages (i) or at least one purification stage (P) can be carried out only on conclusion of the last stage (i).

[0145] The term "a purification stage (P) or a purification (P) carried out in an aqueous reaction medium” is understood to mean, within the meaning of the present invention, a purification stage (P) or a purification (P) carried out in any aqueous medium preferentially devoid of any water-miscible organic solvent and comprising at least one compound of formula (IV), which can result from the reaction stage (i) and / or from at least one reaction stage (ii), preferably in an aqueous medium devoid of any organic solvent.

[0146] Thus, the purification (P) is carried out in an aqueous reaction medium, comprising at least one compound of formula (IV), which is preferentially devoid of any water-miscible organic solvent, that is to say in an aqueous medium not comprising a water-miscible organic solvent.

[0147] In other words, the treatment stage(s) (Pl) and the separation stage(s) (P2) are carried out in an aqueous reaction medium preferentially devoid of any water-miscible organic solvent and comprising at least one compound of formula (IV) and / or (IV).

[0148] In other words, the treatment stage (Pl) and the separation stage (P2) preferentially do not employ a water-miscible organic solvent.

[0149] Preferably, the purification (P) is carried out in an aqueous reaction medium devoid of any organic solvent.

[0150] In other words, the purification (P) is preferentially carried out in water.

[0151] In other words, the treatment stage (Pl) and the separation stage (P2) preferentially do not employ an organic solvent.

[0152] According to a preferred characteristic of the present invention, the purification (P) is devoid of any stage or operation of washing with at least one water- miscible organic solvent, preferably of any stage or operation of washing with at least one organic solvent.

[0153] More preferentially still, the purification (P) does not employ an organic solvent chosen from the group consisting of dichloromethane, diethyl ether, ethanol and their mixtures.

[0154] In particular, the purification (P) does not employ an organic solvent chosen from the group consisting of ethanol, methanol, isopropanol, butanol, isobutanol, tertbutanol and their mixtures.

[0155] According to one embodiment, the reaction medium of the purification stage (P) does not comprise at least one organic solvent as defined above, in particular chosen from the group consisting of di chloromethane, ethanol, methanol, toluene, isopropanol and their mixtures, especially dichloromethane, ethanol and their mixtures.

[0156] According to one embodiment, the purification (P) does not employ an organic solvent chosen from the group consisting of dichloromethane, diethyl ether, ethanol, methanol, isopropanol, butanol, isobutanol, tert-butanol, toluene, isopropanol and their mixtures.

[0157] More particularly, the purification (P) does not employ an organic solvent chosen from the group consisting of non-polar aprotic organic solvents, such as those described above, C1-C3 alcohols, and their mixtures.

[0158] The purification (P) is in particular devoid of an organic solvent chosen from the group consisting of heptane, 1,4-di oxane, benzene, xylene, tetrachloroethylene (C12C=CC12), toluene, carbon disulfide (CS2), trichloroethylene (C12C=CHC1), diethyl ether (Et2O), diisopropyl ether, tert-butyl methyl ether, ethyl acetate (CH3C(O)OEt or AcOEt), butyl acetate, isopropyl acetate, methylpyrrolidone, cyclopentyl methyl ether, ketones, such as methyl ether ketone or methyl isobutyl ketone, methyl propionate, butanol, isobutanol, tert-butanol, pentanol, dimethyl ether (DME), tetrahydrofuran (THF), methyltetrahydrofuran (2-MeTHF), dichloromethane (CH2Q2), di chloroethane (CICH2CH2CI) and their mixtures.

[0159] The purification (P) is in particular devoid of a (non-)polar aprotic organic solvent, such as non-polar aprotic organic solvents, preferably having a dielectric constant ranging from 1 to 11.

[0160] The purification (P) is more particularly devoid of a (non-)polar (a)protic organic solvent.

[0161] According to a general characteristic of the invention, the purification stage (P) is in particular devoid of at least one stage of washing the reaction medium, resulting from a stage (i) and / or resulting from at least one stage (ii), carried out with at least one organic solvent as defined above.

[0162] Preferably, on conclusion of the reaction stage(s) (i) and / or on conclusion of at least one reaction stage (ii), the process does not comprise at least one stage of washing the reaction medium carried out with at least one organic solvent as defined above.

[0163] Thus, in accordance with one advantage of the present invention, no treatment stage (Pl) is carried out in addition to at least one stage of washing with at least one organic solvent, preferably at least one organic solvent as defined above.

[0164] Treatment stage (Pl)

[0165] The stage(s) of treatment (Pl) of the reaction medium comprising at least one compound of formula (IV) are carried out with at least one cationic ion-exchange resin, preferably at least one weak cationic resin, for example a resin having carboxylic active groups, and / or at least one strong cationic resin, preferably at least one sulfonic resin.

[0166] In other words, the aqueous reaction medium, which can result from at least one stage (i) and / or from at least one stage (ii), is brought into contact with at least one cationic ion-exchange resin, preferably at least one weak cationic resin, for example a resin having carboxylic active groups, and / or at least one strong cationic resin, preferably at least one sulfonic resin.

[0167] Preferably, the treatment stage(s) (Pl) are carried out with at least one cationic resin having carboxylic groups and / or at least one sulfonic resin, preferably at least one sulfonic resin.

[0168] Preferably, the treatment stage(s) (Pl) are carried out with at least one cationic resin comprising one or more carboxylic groups and / or one or more sulfonic groups.

[0169] Preferably, the stage(s) of treatment (Pl) of the reaction medium comprising at least one compound of formula (IV) are carried out with at least one sulfonic resin.

[0170] Preferably, the cationic ion-exchange resin is a sulfonic resin comprising one or more sulfonic (SO3H) groups and / or one or more sulfonate (-SO3 ) groups, more preferably one or more sulfonate (-SOf) groups.

[0171] The treatment stage(s) (Pl) are carried out at a pH value strictly lower than the pKa of the compound corresponding to the formula (IV).

[0172] When the reaction medium to be treated by at least one treatment stage (Pl) contains several different compounds of formula (IV), the treatment stage(s) (Pl) are carried out at a pH value strictly lower than the lowest pKa of the pKa values of the compounds of formula (IV).

[0173] When the process comprises several stages (i), the treatment stage (Pl) can be carried out on conclusion of each stage (i) or on conclusion of the last stage (i).

[0174] When the process comprises several stages (ii), the treatment stage (Pl) can be carried out on conclusion of each stage (ii) or on conclusion of the last stage (ii).

[0175] According to one embodiment, the process comprises a single stage (i) and the stage (Pl) is carried out at least once on conclusion of stage (i).

[0176] According to another embodiment, the process comprises a single stage (ii) and the stage (Pl) is carried out at least once on conclusion of stage (ii).

[0177] According to a preferred embodiment, the process comprises a single stage (i) and a single stage (ii) and the stage (Pl) is carried out one or more times between stage (i) and stage (ii), preferably once. Preferably, the stage(s) of treatment (Pl) of the reaction medium resulting from the reaction stage (i) is / are carried out in a pH range extending from 1.5 to 6, preferably extending from 2 to 4.5, more preferentially extending from 2 to 3.5, better still in a pH range extending from 2.5 to 3.5.

[0178] The treatment stage (Pl) can be carried out one or more times, preferably once.

[0179] Separation stage (P2)

[0180] The separation stage(s) (P2) can be carried out immediately after the stage(s) (Pl).

[0181] According to one embodiment, the stages (Pl) and (P2) are carried out successively on conclusion of at least one stage (i).

[0182] According to another embodiment, the stages (Pl) and (P2) are carried out successively on conclusion of at least one stage (ii).

[0183] According to yet another embodiment, at least one stage (Pl) is carried out on conclusion of at least one stage (i), and at least one stage (P2) is carried out on conclusion of at least one stage (ii).

[0184] According to another embodiment, the process of the invention carries out at least one stage (Pl) on conclusion of at least one stage (i) and carries out at least one stage (P2) on conclusion of at least one stage (i) and on conclusion of at least one stage (ii).

[0185] Preferably, the separation stage(s) (P2) are carried out by distillation or electrodialysis, preferably by vacuum distillation, more preferentially by vacuum distillation at a temperature capable of varying from 30°C to 80°C, preferably from 30°C to 55°C, preferably from 30°C to 50°C.

[0186] Preferably, the stage(s) of separation (P2) of at least said compound of formula (IV') from the reaction medium resulting from stage (Pl) is / are carried out by distillation or electrodialysis, preferably by vacuum distillation.

[0187] Preferably, the stage(s) of separation (P2) of at least said compound of formula (IV') from the reaction medium resulting from stage (Pl) is / are carried out by distillation, preferably by vacuum distillation, at a temperature capable of varying from 30°C to 80°C, preferably from 30°C to 55°C, preferably from 30°C to 50°C.

[0188] According to one embodiment, the separation stage (P2) can be carried out several times. The separation stage (P2), preferably a distillation, is advantageously carried out several times depending on the content of impurities (IV') which it is desired to achieve in the composition comprising the compound of formula (I).

[0189] In other words, the separation stage (P2), preferably a distillation, can advantageously be carried out depending on the grade of the compound(s) of formula (I) which it is desired to obtain.

[0190] Preferably, on conclusion of the separation stage (P2) or of the last purification stage (P2), the content of compound(s) of formula (IV) is less than or equal to 10% by weight, preferably is less than or equal to 5% by weight, more preferentially varies from 1% to 5% by weight, better still varies from 1% to 2% by weight, with respect to the total weight of the dry extract containing the compound(s) of formula (I).

[0191] On conclusion of the separation stage (P2) or of the last separation stage (P2), the content of the compound(s) of formula (IA) varies from 20% to 70%, preferably from 30% to 60%, by weight, with respect to the total weight of the dry extract.

[0192] According to one embodiment, water can be added between the treatment stage (Pl) or the last treatment stage (Pl) and at least one separation stage (P2).

[0193] Preferably, on conclusion of the treatment stage (Pl) or of the last treatment stage (Pl), water can be added and the separation stage (P2), preferably a distillation, is carried out at least once to separate at least the compound of formula (IV') and the water from the reaction medium.

[0194] Preferably, the addition of water and the separation stage (P2) can be carried out several times, which makes it possible to facilitate the separation of the compound of formula (IV) from the reaction medium.

[0195] Additional stages during the purification stage (P)

[0196] The purification (P) can also comprise one or more additional stages, different from the stages (Pl) and (P2).

[0197] The purification (P), carried out in an aqueous reaction medium comprising at least the compound of formula (IV), can comprise, simultaneously or sequentially, preferably sequentially, in particular before or after the treatment stage (Pl), in particular before the treatment stage (Pl), at least one stage of neutralisation (P0) of all or part of the excess alkaline agent present in the reaction medium resulting from stage (i). Preferably, the at least one purification (P), carried out in an aqueous reaction medium, comprises:

[0198] ■ at least one treatment stage (PO) to neutralise all or part of the excess alkaline agent present in the reaction medium resulting from the at least one stage (i),

[0199] ■ at least one stage of treatment (Pl) of the reaction medium resulting from stage (i) with at least one cationic ion-exchange resin, as defined above, carried out at a pH value strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), if several are present,

[0200] ■ at least one stage of separation (P2) of at least said compound(s) of formula (IV) from the reaction medium,

[0201] ■ optionally, at least one stage of separation (P'O) of the compound(s) of formula (III) present in the reaction medium on conclusion of the reaction(s) (i).

[0202] The purification stage (P) optionally additionally comprises at least one stage of activation of the cationic ion-exchange resin in order for it to be in acid form.

[0203] The stage of activation of the resin can be carried out before the neutralisation stage (PO) and / or before the treatment stage (Pl).

[0204] According to one embodiment, the neutralisation stage (PO) is carried out with at least one cationic ion-exchange resin at a pH value strictly lower than the pKa of the compound of formula (IV') or by adding at least one acidifying agent which is organic or mineral, preferably mineral, and more preferentially chosen from the group consisting of mineral acids as described above, to the reaction medium resulting from stage (i).

[0205] Preferably, the stage of neutralisation (PO) of all or part of the excess alkaline agent is carried out with at least one cationic ion-exchange resin at a pH value strictly lower than the pKa of the compound of formula (IV') or at a value strictly lower than the lowest pKa of said compounds of formula (IV), preferably in a pH range extending from 1.5 to 6, preferably extending from 2 to 4.5, more preferentially extending from 2 to 3.5, better still in a pH range extending from 2.5 to 3.5.

[0206] The cationic ion-exchange resin, capable of being employed during the treatment stage (PO), can be identical to or different from, preferably identical to, that employed in the treatment stage (Pl). In an alternative form, the stage of neutralisation (P0) of all or part of the at least one alkaline agent can be carried out by adding at least one organic or mineral, preferably mineral, acidifying agent to the reaction medium resulting from stage (i).

[0207] Preferably, the stage of separation (P'O) of the compound of formula (III) is carried out after the neutralisation stage (PO).

[0208] More preferentially, the stage of separation (P'O) of the compound of formula (III) can be carried out by distillation.

[0209] Before the optional implementation of at least one reaction stage (ii), the pH of the reaction medium can be modified by addition of at least one mineral acidifying agent or of a mineral or organic alkaline agent.

[0210] Preferably, the pH of the reaction medium can be modified by addition of at least one mineral acidifying agent, in particular of mineral acid type, such as sulfuric acid, phosphoric acid, sulfonic acid, phosphonic acid, the H Hal" acids with Hal representing a halogen atom chosen from the group consisting of chlorine, bromine and iodine; more preferentially, the acidifying agent is hydrochloric acid.

[0211] Reaction stage (ii)

[0212] The preparation process can optionally additionally comprise at least one stage of reaction (ii) of at least said compound of formula (I) in which X corresponds to a divalent radical -C(O)- (i.e. a compound of formula (IA)) to form at least one compound of formula (I) in which X corresponds to a divalent radical -CH(OR)- (i.e. a compound of formula (IB)).

[0213] According to an advantageous embodiment, the process according to the invention additionally comprises at least one stage of reaction (ii) of at least said compound of formula (IA) to form at least one compound of formula (IB).

[0214] Reduction stage (iil)

[0215] The reaction stage (ii) is preferably a reduction stage (iil) taking place in an aqueous medium according to the following synthetic pathway (B): in which synthetic pathway (B):

[0216] ■ SA' and Ri have the same meanings as in the formula (I).

[0217] Within the meaning of the present invention, a compound of formula (I'B) is a compound of formula (IB) in which R represents a hydrogen atom.

[0218] In other words, a compound of formula (I'B) is a compound of formula (I) in which X corresponds to a divalent radical -CH(OR)- with R representing a hydrogen atom.

[0219] Preferably, the preparation process according to the invention comprises: at least one reaction stage (i), as described above, at least one reduction stage (ii 1), which takes place in an aqueous medium according to the synthetic pathway (B) as defined above, at least one purification stage (P), as described above, carried out before and / or after the reduction stage (iil).

[0220] The stage of reduction of the carbonyl group in order to result in an alcohol group is carried out by a conventional reduction method known to a person skilled in the art. Mention may be made, for example, of the work Adv. Org. Chem.. J. March, 4th Ed., John Wiley & Son, pp. 910-919 (1992). The at least one reduction stage (iil) can be a reduction carried out in the presence of one or more hydrides, in particular borohydrides, such as NaBEE or NaBHjCN, an enzymatic reduction or a reduction by catalytic hydrogenation.

[0221] Preferably, the at least one reduction stage (iil) is a reduction by catalytic hydrogenation.

[0222] In other words, the at least one reduction stage (iil) is advantageously a hydrogenation carried out in the presence of at least one catalyst and optionally of an acidifying agent. The hydrogenation can, for example, be carried out under conditions described in the literature (Heterocycles, M. Hashimoto and M. Takahashi, 77 (1), 227- 231 (2009)).

[0223] The catalyst is preferably a metal catalyst, such as ruthenium (Ru), rhodium (Rh), platinum (Pt), iridium (Ir), nickel (Ni) or palladium (Pd), preferably ruthenium (Ru), more preferentially a metal catalyst chosen from ruthenium (Ru), rhodium (Rh), platinum (Pt) or iridium (Ir), better still ruthenium (Ru).

[0224] Preferably, the catalyst is supported, preferentially is supported ruthenium, such as on charcoal (or graphite), on alumina, on Al Si, on zeolite or on barium sulfate (BaSO4). According to one embodiment, the hydrogenation is catalysed by Pd on charcoal (Pd / C) or Ru on charcoal (Ru / C).

[0225] Preferably, the catalyst is chosen from the group consisting of ruthenium on charcoal (Ru / C), ruthenium on alumina (Ru / Al), ruthenium on AlSi, ruthenium on zeolite or ruthenium on barium sulfate (BaSC ).

[0226] Preferentially, the catalyst is ruthenium (Ru), in particular on charcoal (Ru / C).

[0227] Preferably, the at least one reduction stage (iil) is a reduction by catalytic hydrogenation carried out in the presence of at least one metal catalyst, especially ruthenium (Ru).

[0228] Preferably, the at least one reduction stage (iil) is carried out under a hydrogen pressure ranging from 2 to 100 bar, preferably ranging from 3 to 50 bar, more preferentially ranging from 4 to 25 bar, more preferentially still ranging from 5 to 15 bar, better still ranging from 6 to 12 bar, such as 10 bar.

[0229] Preferably, the at least one reduction stage (iil) is carried out at a temperature which can range from 30°C to 150°C, preferably at a temperature ranging from 40°C to 100°C, more preferentially at a temperature ranging from 65°C to 100°C.

[0230] Preferably, the at least one reduction stage (iil) takes place over a period which can range from 30 minutes to 30 hours, preferably from 45 minutes to 10 hours, in particular ranging from 1 hour to 7 hours.

[0231] Preferably, the at least one reduction stage (iil) is a reduction by catalytic hydrogenation in the presence of at least one catalyst, in particular ruthenium, under a hydrogen pressure ranging from 2 to 100 bar and at a temperature ranging from 30°C to 150°C.

[0232] Preferably, the at least one reduction stage (iil) is a reduction by catalytic hydrogenation in the presence of at least one catalyst, in particular ruthenium, under a hydrogen pressure ranging from 2 to 50 bar and at a temperature ranging from 40°C to 100°C.

[0233] Preferably, the at least one reduction stage (iil) is a reduction by catalytic hydrogenation in the presence of at least one catalyst, in particular ruthenium, under a hydrogen pressure ranging from 2 to 25 bar and at a temperature ranging from 65°C to 100°C.

[0234] Advantageously, the at least one reduction stage (iil) is carried out, in an aqueous medium:

[0235] - in the presence: ■ of at least one compound of formula (I), in which X is a divalent radical - C(O)-,

[0236] ■ of at least one catalyst, more preferentially chosen from the group consisting of palladium and ruthenium, in particular ruthenium on charcoal,

[0237] - at a hydrogen pressure varying from 2 to 50 bar, more preferentially from 4 to 12 bar, such as 10 bar;

[0238] - at a temperature which can range from 40°C to 100°C, preferably at a temperature ranging from 65°C to 120°C.

[0239] On conclusion of the at least one reduction stage (iil), the reaction medium can be cooled to a temperature varying from 15°C to 25°C and then is purged under nitrogen.

[0240] The reaction medium resulting from stage (iil) is subsequently preferably filtered.

[0241] Preferably, the preparation process according to the invention successively comprises: o at least one reduction stage (iil) as defined above,

[0242] ■ preferably, the reaction medium before, during or on conclusion of the reduction stage (iil) is subjected to at least one treatment with carbon black, more preferentially before or after the reduction stage (iil), in particular before the reduction stage (iil) the reaction medium is subjected to at least one treatment with carbon black, optionally at a temperature which can range from 20°C to 90°C,

[0243] ■ optionally, at least one stage of addition of at least one acidifying or basifying agent to the reaction medium resulting from the reduction stage (iil), o optionally, at least one stage of concentration (iil) of the compound of formula (IB) in the reaction medium resulting from the reduction step (iil),

[0244] ■ preferably, the concentration stage (iil) is carried out by distillation, preferably under reduced pressure, o optionally, at least one purification stage, such as a filtration, o optionally, at least one stage (iv) of addition of at least one bactericidal or bacteriostatic, preferably bacteriostatic, agent, preferably derived from glycol, such as propylene glycol, pentylene glycol or caprylyl glycol, ■ preferably, the bacteriostatic agent, in particular propylene glycol, is present in a content ranging from 2% to 50% by weight, preferentially from 5% to 40% by weight, with respect to the total weight of the mixture comprising at least the compound of formula (IB) and the bacteriostatic agent,

[0245] ■ optionally, at least one purification stage, such as a distillation.

[0246] Within the meaning of the present invention, the term "biobased" is understood to mean that the compounds described as "biobased" result from compounds of plant origin.

[0247] Addition stage (ii2)

[0248] The reaction stage (ii) can also be an addition or O-alkoxylation stage (ii2) taking place in an aqueous or non-aqueous medium according to the following synthetic pathway (Bl): in which synthetic pathway (Bl):

[0249] R corresponds to a Ci-Cio, preferably C1-C4, alkyl group, such as methyl, or a (Ci-C4)alkylcarbonyl group, such as acetyl.

[0250] Advantageously, the process according to the invention comprises: at least one stage (i) as defined above, at least one reaction stage (ii) corresponding to a reduction stage (iil) as defined above, at least one reaction stage (ii) corresponding to an addition stage (ii2) as defined above, at least one purification (P), as defined above, carried out at least between the reaction stage (i) and the reduction stage (iil), and / or at least after the reduction stage (iil), preferably between the reduction stage (iil) and the addition stage (ii2), and / or after the addition stage (ii2).

[0251] According to another alternative form of the invention, the compounds (I"B) are obtained by addition of at least one molar equivalent of at least one nucleophilic compound R-G to at least one compound of formula (IA), with R as defined above and G representing an electrodeficient atom or group, such as an alkali metal, such as sodium, potassium or lithium, or else a magnesium halide, such as MgCl in particular this reaction is carried out under an inert atmosphere and in a solvent, preferably a polar aprotic organic solvent, particularly an ethereal solvent, such as diethyl ether or THF, followed by a hydrolysis reaction.

[0252] Packaging of the compound of formula (I)

[0253] On conclusion of the process according to the invention, the compound of formula (I), in which X corresponds to a divalent radical -C(O)- or -CH(OR)-, can be packaged in the form of a dry extract (without solvent).

[0254] Preferably, on conclusion of the process according to the invention, the compound of formula (I), in which X corresponds to a divalent radical -C(O)- or - CH(OR)-, is in solution in a liquid which comprises a content of at least 25% by weight of active material of the compound of formula (I), preferentially in a content ranging from 25% to 80% by weight, more preferentially ranging from 25% to 75% by weight, more preferentially ranging from 30% to 75% by weight, with respect to the total weight of the solution.

[0255] Preferably, on conclusion of the process according to the invention, the compound of formula (I), in which X corresponds to a divalent radical -C(O)- or - CH(OR)-, is in solution in a liquid which comprises a content of at least 20% by weight of active material of the compound of formula (I), preferentially in a content ranging from 20% to 90% by weight, more preferentially ranging from 25% to 80% by weight, more preferentially ranging from 25% to 75% by weight, with respect to the total weight of the solution.

[0256] Preferably, on conclusion of the process according to the invention, the compound of formula (I), in which X corresponds to a divalent radical -C(O)- or - CH(OR)-, is in solution in a liquid which comprises a content of at least 25% by weight of active material (I), more preferentially a content ranging from 25% to 45% by weight, with respect to the total weight of the solution.

[0257] Preferably, on conclusion of the process according to the invention, the compound of formula (I), in which X corresponds to a radical -C(O)- or -CH(OR)-, is in solution in a liquid which comprises a content of at least 25% by weight of active material, more preferentially a content ranging from 25% to 75% by weight, with respect to the total weight of the solution. According to one embodiment, the compound of formula (I), in which X corresponds to a divalent radical -C(O)- or -CH(OR)-, is packaged in a liquid and the pH is adjusted to a target value, preferably between 3.5 and 7, by addition of at least one basifying agent or of at least one acidifying agent.

[0258] Chemical structure(s)

[0259] SA' can represent a monosaccharide group or a polysaccharide group comprising up to 6 sugar units, in pyranose and / or furanose form and of the L and / or D series, of a or P anomer, and comprising at least one free hydroxyl group, and optionally at least one optionally protected amine group.

[0260] Preferably, SA' represents a monosaccharide or a polysaccharide comprising up to 6 sugar units, in pyranose and / or furanose form and of the L and / or D series, and comprising at least one free hydroxyl group.

[0261] According to one embodiment, SA' is a monosaccharide group chosen from the group consisting of glucose, galactose, mannose, xylose, fucose, arabinose, rhamnose, glucuronic acid, galacturonic acid, iduronic acid, N-acetylglucosamine and N-acetylgalactosamine and more particularly SA is a monosaccharide chosen from the group consisting of D-glucose, D-galactose, D-mannose, D-xylose, L-fucose, L- arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N- acetyl-D-glucosamine and N-acetyl-D-galactosamine.

[0262] Preferably, SA' is a monosaccharide chosen from the group consisting of glucose, xylose, N-acetylgalactosamine and fucose, in particular glucose, xylose and fucose, more particularly xylose.

[0263] More preferentially, SA' is a monosaccharide group chosen from the group consisting of D-glucose, D-xylose, N-acetyl-D-galactosamine and L-fucose, in particular D-glucose, D-xylose and L-fucose, more particularly D-xylose.

[0264] According to one embodiment, SA' is a polysaccharide group comprising up to 6 sucrose units and chosen from the group consisting of D-maltose, D-lactose, D- cellobiose, D-maltotriose, a disaccharide combining a uronic acid chosen from D- iduronic acid or D-glucuronic acid with a hexosamine chosen from D-galactosamine, D-glucosamine, N-acetyl-D-galactosamine or N-acetyl-D-glucosamine, an oligosaccharide containing at least one xylose advantageously chosen from xylobiose, methyl P-xylobioside, xylotriose, xylotetrose, xylopentose and xylohexose, and preferentially xylobiose, which is composed of two xylose molecules linked via a 0-1- 4 bond.

[0265] Preferably, SA' represents a monosaccharide.

[0266] Preferably, SA' represents a monosaccharide group chosen from the group constituted of glucose, in particular D-glucose, xylose, in particular D-xylose, fucose, in particular L-fucose, arabinose, in particular L-arabinose, rhamnose, in particular L- rhamnose, glucuronic acid, in particular D-glucuronic acid, galacturonic acid, in particular D -galacturonic acid, iduronic acid, in particular D-iduronic acid, N- acetylglucosamine, in particular N-acetyl-D-glucosamine, and N-acetylgalactosamine, in particular N-acetyl-D-galactosamine, and preferably SA' is chosen from D-glucose, D-xylose, L-fucose, L-arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid or D-iduronic acid.

[0267] Preferably, SA' represents a monosaccharide group chosen from the group consisting of glucose, xylose, N-acetylgalactosamine and fucose; more preferentially, SA' is chosen from the group consisting of glucose, xylose and fucose.

[0268] Preferably, SA' represents a monosaccharide group chosen from the group consisting of D-glucose, D-xylose, N-acetyl-D-galactosamine and L-fucose; more preferentially, SA' is chosen from the group consisting of D-glucose, D-xylose and L- fucose.

[0269] More preferentially, SA' represents a xylose group and more preferentially still D-xylose.

[0270] As indicated above, Ri represents a saturated or unsaturated, linear or branched, cyclic or acyclic, Ci-Cio, preferably Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

[0271] According to one embodiment, Ri represents a saturated or unsaturated, linear or branched, cyclic or acyclic, preferably acyclic, Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

[0272] According to one embodiment, Ri represents a saturated or unsaturated, linear or branched, cyclic, such as cyclohexyl or cyclopentyl, or acyclic, Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

[0273] Preferably, Ri represents a saturated or unsaturated, linear or branched, preferably linear, acyclic, C1-C10, preferably Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

[0274] Preferably, Ri represents a saturated or unsaturated, linear, acyclic, C1-C10, preferably Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain. Preferentially, Ri represents a saturated or unsaturated, linear, acyclic, C1-C4, in particular Ci, alkyl chain.

[0275] Preferably, X represents a divalent radical -C(O)- or -CH(OH)-.

[0276] Advantageously, in the formula (I):

[0277] X represents a divalent radical -C(O)- or -CH(OH)-,

[0278] SA' represents a monosaccharide group chosen from the group consisting of D-glucose, D-galactose, D-mannose, D-xylose, L-fucose, L-arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N- acetyl-D-glucosamine and N-acetyl-D-galactosamine, preferably chosen from D-glucose, D-galactose, D-mannose, D-xylose, L-fucose, L- arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid or D- iduronic acid, more preferentially chosen from D-glucose, D-xylose or L- fucose;

[0279] - Ri represents a saturated or unsaturated, linear, acyclic, C1-C10, preferably Ci-Ce, more preferentially C1-C4, hydrocarbon chain, in particular a methyl group.

[0280] According to one embodiment, in the formula (III), Ri and R2 are identical and represent a saturated or unsaturated, linear or branched, cyclic or acyclic, preferably acyclic, Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

[0281] Preferably, in the formula (III), Ri and R2 are identical and represent a saturated or unsaturated, linear or branched, acyclic, Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

[0282] Preferably, in the formula (III), Ri and R2 are identical and represent a saturated or unsaturated, linear, acyclic, C1-C4, in particular Ci, hydrocarbon chain.

[0283] According to one embodiment, in the formula (IV), R2 represents a saturated or unsaturated, linear or branched, cyclic or acyclic, preferably acyclic, Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

[0284] Preferably, in the formula (IV), R2 represents a saturated or unsaturated, linear or branched, acyclic, Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

[0285] Preferably, in the formula (IV), R2 represents a saturated or unsaturated, linear, acyclic, C1-C4, in particular Ci, hydrocarbon chain. Preferably, in the formulae (I), (III) and (IV), Ri and R2 are identical and represent a saturated or unsaturated, linear, acyclic, C1-C10, preferably C1-C4, in particular Ci, hydrocarbon chain.

[0286] According to one embodiment, D can be an organic cation, preferably chosen from the group consisting of ammonium, phosphonium, imadazolium, pyrazolium, piperidinium and piperazinium ions.

[0287] According to one embodiment, D is an inorganic cation chosen from the group consisting of alkali metal cations and alkaline earth metal cations.

[0288] Advantageously, D is a cation chosen from the group consisting of alkali metal cations, alkaline earth metal cations and the ammonium ion (NH ), in particular alkali metal cations and alkaline earth metal cations.

[0289] Preferably, D is a cation chosen from the group consisting of the calcium ion (Ca2+), the magnesium ion (Mg2+), the sodium ion (Na+) and the potassium ion (K+), in particular the calcium ion and the sodium ion, more particularly the sodium ion.

[0290] Advantageously, SA' corresponds to the following formula (If): in which formula (If) the index n is equal to 0 or 1, preferably is equal to 1, and the index p is an integer varying from 1 to 4; preferably, the index p is equal to 3.

[0291] Preferably, in the formula (If), n is equal to 1 and p is an integer varying from 1 to 4; preferably, the index p is equal to 3.

[0292] More preferably, in the formula (IP), n is equal to 1 and p is equal to 3.

[0293] The process for the preparation of at least one compound of formula (I) is preferentially a process for the preparation of at least one compound of following formula (P): in which formula (!'): n is equal to 0 or 1, preferably is equal to 1, p is an integer varying from 1 to 4; preferably, the index p is equal to 3,

[0294] - Ri exhibits the same meaning as in the formula (I), preferably represents a linear, preferably acyclic, Ci-Cio, preferably Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain;

[0295] X represents a divalent radical -C(O)- or -CH(OR)-,

[0296] - R represents a hydrogen atom, a C1-C10, preferably C1-C4, alkyl group, such as methyl, or a (Ci-C4)alkylcarbonyl group, such as acetyl; preferably, R represents a hydrogen atom, and also one of its optical isomers, geometrical isomers, and / or one of its solvates, such as the hydrates, said process comprising: at least one reaction stage (i) taking place according to the following synthesis scheme (A1): in which synthetic pathway (A1): o n is equal to 0 or 1, preferably is equal to 1, o p is an integer varying from 1 to 4; preferably, the index p is equal to 3, o Ri and R2 are identical or different, preferably identical, with R2 having the same meaning as Ri in the formula (!'), o D+is an organic or inorganic cation, preferably an inorganic cation, more preferentially chosen from the group consisting of alkali metal cations, alkaline earth metal cations and the ammonium cation (NH4+), better still from the group consisting of alkali metal cations and alkaline earth metal cations, said reaction stage (i) being carried out in an aqueous medium in the presence: o of at least one compound of formula (If), o of at least one compound of formula (III), preferably present in an equimolar amount or in excess with respect to the compound of formula (If), preferably in excess,

[0297] ■ preferably, the compound(s) of formula (III) / compound(s) of formula (If) molar ratio is greater than or equal to 1, preferably of between 1 and 5, more preferentially between 1 and 4, more particularly still between 1 and 3, better still between 1 and 2, in particular ranging from 1 to 1.5; according to a particular embodiment, the compound(s) of formula (III) / compound(s) of formula (If) molar ratio is greater than 1, o of at least one alkaline agent in an equimolar amount or in excess, preferably in excess, with respect to the compound of formula (If),

[0298] ■ preferably, the alkaline agent(s) / compound(s') of formula (If) molar ratio is greater than or equal to 1, preferably of between 1 and 5, more preferentially between 1 and 4, more particularly still between 1 and 3, better still between 1 and 2; according to a particular embodiment, the alkaline agent / compound of formula (If) molar ratio is greater than 1,

[0299] ■ the alkaline agent preferably being mineral, more preferentially chosen from the group consisting of alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal (bi)carbonates, and their mixtures; in particular alkali metal and alkaline earth metal hydroxides, such as sodium hydroxide, to result in the formation of at least one compound of formula (TAI) and of at least one compound of formula (IV);

[0300] - optionally, at least one stage of reaction (ii) of at least said compound of formula (I'Al) to result in at least one compound corresponding to the formula (I'Bl): in which formula (I'B 1) the indices n and p and Ri have the same meanings as in the formula (I);

[0301] ■ preferably, the reaction stage (ii) is a reduction stage (iil), as defined above, - at least one purification (P) of the reaction medium including at least said compound of formula (IV), carried out in an aqueous medium, successively comprising:

[0302] ■ at least one treatment stage (Pl) carried out with at least one cationic ion-exchange resin in order to convert at least said compound of formula (IV) into a compound of formula (IV) according to the following scheme: said treatment stage (Pl) being carried out at a pH strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), if several are present,

[0303] - at least one stage of separation (P2) of at least said compound of formula (IV) from the reaction medium.

[0304] The reaction stage (i) and the purification stage (P) are as defined above. Preferably, the purification (P) is carried out after the reaction stage (i).

[0305] Preferably, the purification (P) is carried out at least between the reaction stage (i) and at least one reaction stage (ii), and / or at least after at least one reaction stage (ii), for example after one and / or two reaction stages (ii).

[0306] Preferably, the reaction stage (ii) is a reduction stage (iil) taking place in an aqueous medium according to the following synthetic pathway (Bl): in which synthetic pathway (Bl):

[0307] - the index p and Ri have the same meanings as in the formula (I).

[0308] Preferably, the reduction stage (iil) is a reduction by catalytic hydrogenation, as defined above.

[0309] Within the meaning of the present invention, a compound of formula (I'Al) is a compound of formula (f) in which X corresponds to a divalent radical -C(O)-. Within the meaning of the present invention, a compound of formula (I'B 1) is a compound of formula (!') in which X corresponds to a divalent radical - CH(OH)-.

[0310] Preferably, the purification (P) is carried out at least between the reaction stage (i), as described above, and the reduction step (iil), as described above.

[0311] More preferentially still, the process for the preparation of at least one compound of formula (I) is a process for the preparation of at least one compound of following formula (I"): and also one of its optical isomers, geometrical isomers, and / or one of its solvates, such as the hydrates, said process comprising: at least one reaction stage (i) taking place according to the following synthesis scheme

[0312] (A"): in which synthetic pathway (A"): o D+is a cation chosen from the group consisting of alkali metal cations, alkaline earth metal cations and the ammonium ion (NH ); said reaction stage (i) being carried out in an aqueous medium in the presence: o of at least one compound of formula (Ilf), preferably present in an equimolar amount or in excess, with respect to the compound of formula (II"),

[0313] ■ preferably, the compound(s) of formula (III) / compound(s) of formula (II") molar ratio is greater than or equal to 1, preferably of between 1 and 5, more preferentially between 1 and 4, more particularly still between 1 and 3, better still between 1 and 2, in particular ranging from 1 to 1.5; according to a particular embodiment, the compound(s) of formula (III) / compound(s) of formula (II") molar ratio is greater than 1, o of at least one alkaline agent in an equimolar amount or in excess, preferably in excess, with respect to the compound of formula (II"),

[0314] ■ preferably, the alkaline agent(s) / compound(s) of formula (II") molar ratio is greater than or equal to 1, preferably of between 1 and 5, more preferentially between 1 and 4, more particularly still between 1 and 3, better still between 1 and 2; according to a particular embodiment, the alkaline agent / compound of formula (II") molar ratio is greater than 1,

[0315] ■ the alkaline agent preferably being mineral, more preferentially chosen from the group consisting of alkali metal and alkaline earth metal hydroxide, in particular sodium hydroxide, to result in the formation of at least one compound of formula (I" A) and of at least one compound of formula (IV);

[0316] - optionally, at least one stage of reaction (ii) of at least said compound of formula (I" A) to result in at least one compound corresponding to the following formula (I"B):

[0317] • preferably, the reaction stage (ii) is a reduction stage (iil), as defined above,

[0318] - at least one purification (P) of the reaction medium including at least said compound of formula (IV"), carried out in an aqueous medium, successively comprising: • at least one treatment stage (Pl) carried out with at least one cationic ion-exchange resin in order to convert at least said compound of formula (IV") into a compound of formula (IV") according to the following scheme: said treatment stage (Pl) being carried out at a pH strictly lower than the pKa of the compound of formula (IV") or lower than the lowest pKa of the compounds of formula (IV"), if several are present,

[0319] • at least one stage of separation of at least said compound of formula (IV") from the reaction medium.

[0320] The reaction stage (i) and the purification stage (P) are as defined above.

[0321] Preferably, the purification (P) is carried out at least between the reaction stage (i) and at least one reaction stage (ii), and / or at least after at least one reaction stage (ii), for example after one and / or two reaction stages (ii).

[0322] Within the meaning of the present invention, a compound of formula (I" A) is a compound of formula (I") in which X corresponds to a divalent radical -C(O)-.

[0323] Within the meaning of the present invention, a compound of formula (I"B) is a compound of formula (I") in which X corresponds to a divalent radical - CH(OH)-.

[0324] Preferably, the reaction stage (ii) is a reduction stage (iil) taking place in an aqueous medium according to the following synthetic pathway (B"):

[0325] Preferably, the reduction stage (iil) is a reduction by catalytic hydrogenation, as defined above. Preferably, the purification (P) is carried out at least between the reaction stage (i) and at least one reduction stage (iil), and / or at least after at least one reduction stage (iil), for example after one and / or two reaction stages (ii).

[0326] Preferably, a purification (P) is carried out at least between the reaction stage (i) and the reduction stage (iil).

[0327] The process for the preparation of at least one compound of formula (f) or (I") can also comprise the additional stages described for the process for the preparation of at least one compound of formula (I).

[0328] Purification process

[0329] The present invention also relates to a process for the purification of at least one aqueous medium including at least one compound corresponding to the formula (I), as defined above, and at least one compound of formula (IV), as defined above, comprising:

[0330] • at least one treatment stage (Pl) carried out with at least one cationic ionexchange resin in order to convert at least said compound of formula (IV) into a compound of formula (IV) according to the following scheme: said treatment stage (Pl) being carried out at a pH strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), if several are present, and

[0331] • at least one stage of separation (P2) of at least said compound of formula (IV) from the reaction medium.

[0332] The treatment stage (Pl) and the separation stage (P2) are as defined above.

[0333] Within the meaning of the present invention, the term “aqueous medium” is understood to mean any aqueous medium devoid of any water-miscible organic solvent, as defined above, preferably an aqueous medium devoid of any organic solvent.

[0334] Thus, the purification process is carried out in an aqueous medium, devoid of any water-miscible organic solvent, comprising at least one compound of formula (IV), that is to say an aqueous reaction medium not comprising a water-miscible organic solvent, preferably not comprising an organic solvent. In other words, the treatment stage (Pl) and the separation stage (P2) do not employ a water-miscible organic solvent.

[0335] More particularly, the treatment stage(s) (Pl) and the separation stage(s) (P2) do not employ a water-miscible or water-immiscible organic solvent.

[0336] The invention is illustrated in more detail in the following non-limiting examples.

[0337] Examples:

[0338] Example 1 - Preparation of C-fi-D-xylopyranoside-Z-hydroxypropane

[0339] (47% by weight)

[0340] Stage 1: Preparation of a compound of formula

[0341] Water (1.04 kg) is charged to a reactor at 20°C. Heating to 50°C is carried out, then D-xylose (700 g) is charged and stirring is carried out until the medium is homogeneous. The mixture is cooled to a temperature of 15°C and acetylacetone (555 g) is charged. The 50% sodium hydroxide solution (540 g) is charged at a temperature of less than 45°C. The mixture is subsequently heated from 30°C to 50°C for a period of time of 30 minutes to 4 hours, then optionally cooled to 20°C and passed through the strong sulfonic ion-exchange resin until the pH is between 2.5 and 3.5.

[0342] Several cycles of addition of water and of distillations of water are subsequently carried out until an acetic acid content of less than 10 000 ppm, indeed even of less than or equal to 6000 ppm, and a dry extract of 30% to 60% are obtained. The pH is subsequently adjusted to 6.0-7.0.

[0343] The product is isolated in solution with a yield of 90-95%. Stage 2: Catalytic hydrogenation in order to obtain the compound of formula (1'1)

[0344] The compound of formula (!') (2.08 kg) in aqueous solution with the appropriate acetic acid content is introduced into a hydrogenator with ruthenium on charcoal (catalytic amount). The mixture is purged at least once with nitrogen and then with hydrogen. The mixture can be heated to a temperature of greater than 25 °C and then hydrogen is introduced under pressure up to a pressure of approximately 10 bar.

[0345] The mixture is heated to a temperature of less than or equal to 100°C for a period of time ranging from 2 to 7 hours under a pressure ranging from 8 to 12 bar.

[0346] The hydrogenation reaction is carried out until the end of the consumption of the hydrogen.

[0347] The reaction medium can be left to return to ambient temperature (20°C) and is then optionally purged with an inert gas (nitrogen). The catalyst is subsequently filtered off and the filtrate is subsequently optionally brought into contact with carbon black. The solution is concentrated until a dry extract of 40% to 80% is obtained.

[0348] The pH of the filtrate is adjusted to acidic pH (for example between 4 and 6).

[0349] A glycol derivative, such as propylene glycol, can be added as solvent to the above solution in order to obtain a content of compound of formula (I) of 20% to 90%.

[0350] The product is isolated in solution with a good yield (between 90-95%) and an acetic acid content of the solution of less than 20 000 ppm.

Claims

CLAIMS1. Process for the preparation of at least one compound of following formula(I):in which formula (I):- SA' represents a monosaccharide group or a polysaccharide group comprising up to 20 sugar units, in particular up to 6 sugar units, in pyranose and / or furanose form and of the L and / or D series, said monosaccharide group or polysaccharide group having at least one substituted free hydroxyl group, and optionally at least one optionally protected amine group,- the bond between SA' and CH2-X is a bond of C-anomeric nature,- X represents a divalent radical -CH(OR)-,- R represents a hydrogen atom, a C1-C10, preferably C1-C4, alkyl group, such as methyl, or a (Ci-C4)alkylcarbonyl group, such as acetyl, preferably a hydrogen atom,- Ri represents a saturated or unsaturated, linear or branched, cyclic or acyclic, preferably acyclic, C1-C10, preferably C1-C4, more preferentially saturated, hydrocarbon chain, and also one of its optical isomers, geometrical isomers, and / or one of its solvates, such as the hydrates, said process comprising: at least one reaction stage (i) taking place according to the following synthesis scheme (A):in which synthetic pathway (A):■ Ri and R2 are identical or different, with R2 having the same meaning as Ri in the formula (I),■ SA' has the same meaning as in the formula (I),■ D+is an organic or inorganic cation resulting from the alkaline agent; preferably, D+is an inorganic cation; said reaction stage (i) being carried out in an aqueous media in the presence:■ of at least one compound of formula (II),■ of at least one compound of formula (III), and■ of at least one alkaline agent in an equimolar amount or in excess, with respect to the compound of formula (II), preferably in excess, to result in the formation of at least one compound of formula (IA) and of at least one compound of formula (IV), at least one stage of reaction (ii) of at least said compound of formula (IA), in a preferably aqueous medium, to result in the formation of at least one compound corresponding to the following formula (IB):(IB) in which formula (IB) SA', Ri and R have the same meanings as in the formula (I); the reaction stage (ii) is at least one stage of reduction (iil) by catalytic hydrogenation carried out in the presence of at least one metal catalyst,- at least one purification (P) of the reaction medium including at least said compound of formula (IV), carried out in an aqueous medium, comprising: o at least one treatment stage (Pl) carried out with at least one cationic ion-exchange resin in order to convert at least said compound of formula (IV) into a compound of formula (IV) according to the following scheme:said treatment stage (Pl) being carried out at a pH strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), if several are present, o at least one stage of separation (P2) of at least said compound of formula (IV) from the reaction medium.

2. Process according to Claim 1, characterised in that the reaction stage (i) is carried out in an aqueous medium in the presence: o of at least one compound of formula (II), o of at least one compound of formula (III),■ preferably, the compound(s) of formula (III) / compound(s) of formula (II) molar ratio is greater than or equal to 1, preferably of between 1 and 5, more preferentially between 1 and 4, more particularly still between 1 and 3, better still between 1 and 2, in particular ranging from 1 to 1.5; in particular, the compound(s) of formula (III) / compound(s) of formula (II) molar ratio is greater than 1; o of at least one mineral alkaline agent, preferentially chosen from the group consisting of alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal (bi)carbonates, and their mixtures; in particular alkali metal and alkaline earth metal hydroxides, such as sodium hydroxide,■ as the alkaline agent is in an equimolar amount or in excess, preferably the alkaline agent(s) / compound(s) of formula (II) molar ratio is greater than or equal to 1, preferably of between 1 and 5, more preferentially between 1 and 4, more particularly still between 1 and 3, better still between 1 and 2, o preferably, the reaction stage (i) takes place:■ at a temperature ranging from 20°C to 80°C, preferably at a temperature ranging from 20°C to 70°C, more preferentially at a temperature ranging from 30°C to 70°C, better still from 30°C to 60°C, even better still at a temperature ranging from 35°C to 45°C; o preferably, the duration of the reaction varies:■ from 10 minutes to 10 hours, preferably from 20 minutes to 5 hours, more preferentially from 30 minutes to 4 hours, more preferentially still from 45 minutes to 3 hours.

3. Process according to Claim 1 or 2, characterised in that the purification(s) (P) can be carried out at least once between a reaction stage (i) and at least one reaction stage (ii), and / or at least once after at least one reaction stage (ii); preferably, the purification (P) is carried out at least once on conclusion of the reaction stage(s) (i).

4. Process according to any one of the preceding claims, characterised in that the purification (P) is carried out in an aqueous reaction medium comprising at least said compound of formula (IV) and devoid of any water-miscible organic solvent, preferably devoid of organic solvent chosen from the group consisting of dichloromethane, diethyl ether, ethanol, methanol, isopropanol, butanol, isobutanol, tert-butanol, toluene, isopropanol and their mixtures, more preferentially devoid of any organic solvent.

5. Process according to any one of the preceding claims, characterised in that the treatment stage(s) (Pl) is or are carried out with at least one cationic resin having carboxylic groups and / or at least one sulfonic resin, preferably at least one sulfonic resin.

6. Process according to any one of the preceding claims, characterised in that the treatment stage(s) (Pl) is or are carried out at a pH ranging from 1.5 to 6, preferably ranging from 2 to 4.5, more preferentially ranging from 2 to 3.5, better still in a pH range extending from 2.5 to 3.5.

7. Process according to any one of the preceding claims, characterised in that the separation stage(s) (P2) is or are carried out by distillation or electrodialysis, preferably by vacuum distillation, more preferentially by vacuum distillation at a temperature varying from 30°C to 80°C, preferably from 30°C to 55 °C, preferably from 30°C to 50°C.

8. Process according to any one of the preceding claims, characterised in that, on conclusion of the separation stage (P2), the content of compound(s) of formula (IV) is less than or equal to 10% by weight, preferably is less than or equal to 5% by weight, more preferentially varies from 1% to 5% by weight, better still varies from 1% to 2% by weight, with respect to the total weight of the dry extract containing the compound(s) of formula (I).

9. Process according to any one of the preceding claims, characterised in that the purification (P) comprises, simultaneously or sequentially, preferably sequentially,in particular before or after the treatment stage (Pl), more preferentially before the treatment stage (Pl), at least one stage of neutralisation (P0) of all or part of the excess alkaline agent present in the reaction medium resulting from stage (i).

10. Process according to any one of the preceding claims, characterised in that the at least one purification stage (P), carried out in an aqueous reaction medium, comprises: o at least one treatment stage (P0) to neutralise all or part of the excess alkaline agent present in the reaction medium resulting from the at least one stage (i), o at least one stage of treatment (Pl) of the reaction medium resulting from stage (i) with at least one cationic ion-exchange resin carried out at a pH value strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), o at least one stage of separation (P2) of at least said compound(s) of formula (IV) from the reaction medium, o at least one stage of separation (P'O) of the compound(s) of formula (III) present in the reaction medium on conclusion of the reaction(s) (i).

11. Process according to Claim 9 or 10, characterised in that the neutralisation stage (P0) can be carried out with at least one cationic ion-exchange resin at a pH value strictly lower than the pKa of the compound of formula (IV) or by adding at least one organic or mineral, preferably mineral, acidifying agent to the reaction medium resulting from stage (i).

12. Process according to any one of the preceding claims, characterised in that the reaction stage (ii) is a reduction stage (iil) taking place in an aqueous medium according to the following synthetic pathway (B):Reductionin which synthetic pathway (B):■ SA' and Ri have the same meanings as in the formula (I).

13. Process according to Claim 12, characterised in that the reaction stage (ii) is at least one stage of reduction (iil) by catalytic hydrogenation, carried out in the presence of at least one metal catalyst chosen from ruthenium (Ru), nickel (Ni) or palladium (Pd).

14. Process according to any one of the preceding claims, characterised in that the compound of formula (I), in which X corresponds to a divalent radical - CH(OR)-, is in solution in a liquid which comprises a content of at least 25% by weight of active material (I), preferably in a content ranging from 25% to 80% by weight, more preferentially ranging from 25% to 75% by weight, more preferentially ranging from 30% to 75% by weight, with respect to the total weight of the solution.

15. Process according to any one of the preceding claims, characterised in that it comprises at least one stage (iv) of addition of at least one bactericidal or bacteriostatic, preferably bacteriostatic, agent, preferably derived from glycol, such as propylene glycol, pentylene glycol or caprylyl glycol.

16. Process according to any one of the preceding claims, characterised in that SA' represents a monosaccharide group chosen from the group constituted of glucose, in particular D-glucose, xylose, in particular D-xylose, fucose, in particular L-fucose, arabinose, in particular L-arabinose, rhamnose, in particular L-rhamnose, glucuronic acid, in particular D-glucuronic acid, galacturonic acid, in particular D- galacturonic acid, iduronic acid, in particular D-iduronic acid, N-acetylglucosamine, in particular N-acetyl-D-glucosamine, and N-acetylgalactosamine, in particular N- acetyl-D-galactosamine, and preferably SA' is chosen from D-glucose, D-xylose, L- fucose, L-arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid or D- iduronic acid.

17. Process according to any one of the preceding claims, characterised in that Ri represents a saturated or unsaturated, linear or branched, cyclic or acyclic, Ci- Cio, preferably Ci-Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

18. Process according to any one of the preceding claims, characterised in thatRi and R2 are identical and represent a saturated or unsaturated, linear, acyclic, Ci- Ce, more preferentially C1-C4, in particular Ci, hydrocarbon chain.

19. Process according to any one of the preceding claims, characterised in that X represents a divalent radical -CH(OH)-.

20. Process according to any one of the preceding claims, characterised in that D+is a cation chosen from the group consisting of alkali metal cations, alkaline earth metal cations and the ammonium ion (NH4+), preferably alkali metal cations and alkaline earth metal cations, in particular from the group consisting of the calcium ion (Ca2+), the magnesium ion (Mg2+), the sodium ion (Na+) and the potassium ion (K+).

21. Process for the purification of at least one aqueous medium including at least one compound of formula (I), as defined according to any one of Claims 1, 16,and 19, and at least one compound of formula (IV), as defined according to Claim or 20, successively comprising: at least one treatment stage (Pl) carried out with at least one cationic ionexchange resin in order to convert at least said compound of formula (IV) into a compound of formula (IV) according to the following scheme:(V)(Wsaid treatment stage (Pl) being carried out at a pH strictly lower than the pKa of the compound of formula (IV) or lower than the lowest pKa of the compounds of formula (IV), if several are present, and at least one stage of separation (P2) of at least said compound of formula (IV) from the reaction medium, at least one stage of reduction (iil) by catalytic hydrogenation carried out in the presence of at least one metal catalyst.

Images