Reduction of acetoacetate esters in the presence of amines

Abstract

The invention relates to the reduction of acetoacetate esters in the presence of amines, to compositions comprising at least two different β-hydroxybutyrate esters and to the use of activated carbon to purify a mixture comprising β-hydroxybutyrate esters and an amine and optionally a catalyst.

Description

[0001] Reduction of acetoacetate esters in the presence of amines

[0002] Background

[0003] The invention relates to the reduction of acetoacetate esters in the presence of amines, to compositions comprising at least two different p-hydroxybutyrate esters and to the use of activated carbon to purify a mixture comprising p-hydroxybutyrate esters and an amine and optionally a catalyst.

[0004] Acetoacetate esters and beta-hydroxy butyric acid (also referred to as “p-hydroxybutyrate”; p-hy- droxyl butyric acid ester; befa-hydroxybutyl; BHB) esters prepared therefrom are valuable compounds with a versatile utilization for example as parenteral nutrients or for the treatment of certain diseases, such as migraine, Parkinson's, Alzheimer’s, and any other diseases related to the ketone metabolism of the brain.

[0005] US 2019 / 117612 A1 pertains to the field of migraine headaches and the management of the symp- tomology thereof using 3-hydroxybutyrate glycerides. US 2018 / 193300 A1 pertains to a method of treatment of mild to moderate non-penetrating closed traumatic brain injury and mild to moderate traumatic brain injury due to surgical intervention using 3-hydroxybutyate glycerides.

[0006] Hence, ketone bodies like acetoacetate (AA) and p-hydroxybutyrate (BHB) are believed to have a positive impact on brain health and may alleviate brain related disease and the associated symptoms. Therefore, it can be beneficial to supplement AA and / or BHB to improve health of a subject such as brain health.

[0007] In the human body, AA and BHB are in a natural equilibrium wherein the interconversion of AA to BHB and BHB to AA is catalysed by the enzyme p-hydroxybutyrate dehydrogenase involving nicotinamide adenine dinucleotide (NAD) (cf. for example H. Kolb et al. “Ketone bodies: from enemy to friend and guardian angel”, BMC Med., 2021 , 19(1), 313). The naturally occurring p-hydroxybutyrate form is the enantiopure R-p-hydroxybutyrate, which is the actual active form. However, in respects to potential diabetes treatment there are beneficial effects of the S-enantiomeric form described (A. Buga et. al. “Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy- controlled ketogenic diet, supplemented with racemic R / S-BHB salts” Clinical Nutrition, Volume 54, 2023, P227-287). Therefore it is highly desirable to have synthetic methods in place, to selectively synthesis the R-enantiomer or the S-enantiomer, either in an enantiopure or enantioenriched version.

[0008] In view of the natural equilibrium between AA and BHB in the human body, it can be desirable to supplement AA and BHB at the same time in order to maintain and respect the natural physiological equilibrium between BHB and AA when supplementing ketone bodies.

[0009] In general, molecules comprising AA units are accessible via e.g. reacting diketene with an organic polyol or a p-hydroxyl butyric acid ester of an organic polyol (WO 2023 / 094654). The respective AA units can be reduced in order to obtain BHB units. So far, it is however necessary to purify the AA- based starting material, e.g. to separate the starting material from amines that may still be present in the crude product mixture, to perform a sufficient reduction.

[0010] Against this background, there is an ongoing need for excellent processes for the synthesis of (poly)alcohols comprising BHB (p-hydroxybutyrate esters). In particular, there is a need for efficient processes for the synthesis of (poly)alcohols comprising BHB that suitably are applicable under industrial scale. Further, there is a need for processes for the synthesis of (poly)alcohols comprising BHB in an enantiomeric excess such as in R-configuration. Further, there is a need for economic processes for the synthesis of said (poly)alcohols comprising BHB. Further, there is a need for compositions comprising (poly)alcohols comprising BHB and additional hydroxyl groups that allow further functionalization at different positions, as well as for an efficient processes for the synthesis of said compositions.

[0011] Summary

[0012] The present invention relates in a first aspect to a process for reducing at least two different acetoacetate esters comprising the step of a) contacting a mixture (M1) comprising a composition (C-AAE) comprising the at least two different acetoacetate esters with a hydrogen source in the presence of a catalyst to obtain a mixture (M2) comprising a composition (C-BHB) comprising at least two different p-hydroxybutyrate esters, wherein the mixture (M1) comprises an amine and wherein one of the at least two different acetoacetate esters does not comprise a hydroxyl group.

[0013] The present invention relates in a second aspect to a composition (C-BHB) comprising at least two different p-hydroxybutyrate esters of formula 2

[0014] wherein

[0015] A is derived from an organic polyol, x is at least 1 , y is 0 or at least 1 , n is 0 or 1 , wherein one of the at least two different p-hydroxybutyrate esters of formula 2, is a compound of formula 2-i, wherein x is the number of hydroxyl groups of the initial organic polyol A and y is 0.

[0016] The present invention relates in a third aspect to the use of activated carbon to purify a mixture comprising a composition (C-BHB) comprising at least two different p-hydroxybutyrate esters and an amine, and optionally a catalyst, wherein one of the at least two different p-hydroxybutyrate esters does not comprise a hydroxyl group.

[0017] The inventors surprisingly found that the novel process and use offer an efficient process of manufacturing (poly)alcohols comprising BHB, wherein the presence of amine is well tolerated.

[0018] Detailed Description

[0019] In the following, the invention will be explained in more detail.

[0020] In order for the present invention to be readily understood, several definitions of terms used in the course of the invention are set forth below.

[0021] According to the present invention, the term “linear or branched C2-12 alkyl” refers to a straight- chained or branched saturated hydrocarbon group having 2 to 12 carbon atoms, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms including methyl, ethyl, propyl, 1 -methylethyl, butyl, 1- methylpropyl, 2-methylpropyl, 1 ,1 -dimethylethyl, pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1 -ethylpropyl, 1 ,1 -dimethylpropyl, 1 ,2-dimethylpropyl, hexyl, 1 -methylpentyl, 2- methylpentyl, 3-methylpentyl, 4-methylpentyl, 1 ,1 -dimethylbutyl, 1 ,2-dimethylbutyl, 1 ,3-dimethyl- butyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1 ,1 ,2-trime- thyl propyl, 1 ,2,2-trimethylpropyl, 1 -ethyl-1 -methylpropyl and 1-ethyl-2-methylpropyl.

[0022] According to the present invention, the term “alkanol” refers to alkyls, wherein at least one, preferably one, hydrogen is substituted with a hydroxyl group. Suitable alkanols are methanol, ethanol, propanol, isopropanol, 1 -buntanol, sec-butyl alcohol, isobutanol, and mixtures thereof.

[0023] According to the present invention, the term “alkyl alkynate” refers to alkyl esters such as acetate esters (also referred to as alkyl acetate) or propionate esters (also referred to as alkyl propionate). Suitable alkyl alkynates are ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, propyl propionate, and mitres thereof.

[0024] According to the present invention, the term “C3-8 cycloalkyl” refers to a monocyclic saturated hydrocarbon group having 3 to 8 carbon ring members, such as 2, 3, 4, 5, 6, 7, or 8 carbon ring members, including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0025] It is to be understood that the linear or branched C2-12 alkyl and C3-8 cycloalkyl may optionally be further substituted. Exemplary substituents include hydroxy, linear or branched C1-12 alkyl, C3-8 cycloalkyl, a carboxy group, halogen, and phenyl.

[0026] According to the present invention, the term “organic polyol” refers to a linear, branched, or cyclic organic compound with generally 2 to 18 carbon atoms having at least two hydroxyl groups, preferably at least three hydroxyl groups. As such, the organic polyol may have 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, or 18 carbon atoms. In some embodiments, no more than one hydroxyl group is connected to one carbon atom. In some embodiments, the organic polyol contains only carbon, hydrogen, and oxygen atoms.

[0027] According to the present invention, the term “at least three hydroxyl groups” means that the respective compound has three or more hydroxyl groups. In some embodiments, “at least three hydroxyl groups” includes 3 to 18 hydroxyl groups such as 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, or 18 hydroxyl groups. In some embodiments, “at least three hydroxyl groups” includes 3 to 12 hydroxyl groups such as 3, 4, 5, 6, 7, 8, 9, 10, 11 , or 12 hydroxyl groups. In some embodiments, “at least three hydroxyl groups” includes 3 to 9 hydroxyl groups such as 3, 4, 5, 6, 7, 8, or 9 hydroxyl groups. In some embodiments, “at least three hydroxyl groups” includes 3 to 6 hydroxyl groups such as 3, 4, 5, or 6 hydroxyl groups. Equally, the term “at least two hydroxyl groups” means that the respective compound has two or more hydroxyl groups. It is to be understood that if not explicitly stated otherwise, all stereoisomers, conformations and configurations are encompassed by compounds and functional groups which can be present as different stereoisomers or in different conformations and configurations. For example, the term “inositol” is to be understood as to include all stereoisomers and conformations such as myo-, scyllo-, muco-, D-chiro-, neo-inositol, L-chiro-, allo-, epi-, and c / s-inositol. For example, the term “hexanetriol” is to be understood as to include all hexane isomers including three hydroxyl groups such as 1 ,1 ,1-hexanetriol, 1 ,1 ,2-hexanetriol, 1 ,2,2-hexanetriol, 1 ,2,3-hexanetriol, 1 ,2,4-hexanetriol, 1 ,2,5- hexanetriol, 1 ,2,6-hexanetriol, 1 ,3,5-hexanetriol, 1 ,3,6-hexanetriol, 2,3,4-hexanetriol, 2,3,5-hex- anetriol etc.

[0028] It is to be understand that denotes the bond of the respective moiety to the remainder of the molecule.

[0029] As used herein, the term “comprising” is to be construed as encompassing both “including” and “consisting of’, both meanings being specifically intended, and hence individually disclosed, embodiments according to the present invention.

[0030] As used herein, the articles “a” and “an” preceding an element or component are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore, “a” or “an” is to be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.

[0031] As used herein, the term “about” modifying the quantity of a substance, ingredient, component, or parameter employed refers to variation in the numerical quantity that can occur, for example, through typical measuring and handling procedures, e.g., liquid handling procedures used for making concentrates or solutions. Furthermore, variation can occur from inadvertent error in measuring procedures, differences in the manufacture, source, or purity of the ingredients employed to carry out the methods, and the like. In some embodiments, the term “about” means within 10% of the reported numerical value. In a more specific embodiment, the term “about” means within 5% or within 2% of the reported numerical value.

[0032] As above-mentioned, the present invention relates in a first aspect to a process for reducing at least two different acetoacetate esters comprising the step of a) contacting a mixture (M1) comprising a composition (C-AAE) comprising the at least two different acetoacetate esters with a hydrogen source in the presence of a catalyst to obtain a mixture (M2) comprising a composition (C-BHB) comprising at least two different p-hydroxybutyrate esters, wherein the mixture (M1) comprises an amine and wherein one of the at least two different acetoacetate esters does not comprise a hydroxyl group.

[0033] The acetoacetate ester that does not comprise a hydroxyl group may be referred to as fully esteri- fied acetoacetate ester. Further, it is to be understood that the amine that is comprised in mixture (M1) and the catalyst are not the same.

[0034] In the following, particular embodiments of the present invention such as ingredients, moieties and reaction conditions are described in further details. It is to be understood that each embodiment is relevant on its own as well as in combination with other embodiments.

[0035] In some embodiments, the amine is a tertiary amine, preferably selected from the group consisting of trimethylamine, trimethylamine (TEA), tripropylamine, 1 ,1 ,3, 3-tetramethylguanidine (TMG), 1 ,4- diazabicyclo[2.2.2]octane (DABCO), N,N-dimethylisopropylamine, 1 ,8-Diazabicyclo(5.4.0)undec-7- ene (DBU), 1 ,5-Diazabicyclo(4.3.0)non-5-ene (DBN), and mixtures thereof, more preferably selected from the group consisting of 1 ,1 ,3, 3-tetramethylguanidine (TMG), 1 ,4-diazabicyclo[2.2.2]oc- tane (DABCO), N,N-dimethylisopropylamine, 1 ,8-Diazabicyclo(5.4.0)undec-7-ene (DBU), 1 ,5-Di- azabicyclo(4.3.0)non-5-ene (DBN), and mixtures thereof, and in particular 1 ,4-diazabicyclo[2.2.2]oc- tane (DABCO).

[0036] In some embodiments, the amine is present in the composition (C-AAE) in amounts of at most about 5 wt.-%, preferably at most about 3 wt.-%, more preferably at most about 2 wt.-%, still more preferably at most about 1 wt.-%, such as at most about 0.5 wt.-% or at most about 0.4 wt.-%, or at most about 0.3 wt.-%, or at most about 0.2 wt.-%, or at most about 0.1 wt.-%, or at most about 0.01 wt.-%, based on the total weight of composition (C-AAE). In some embodiment, the amine is present in the composition (C-AAE) in amounts of at least about 0.00001 wt.-%, or at least about 0.0001 wt.-%, based on the total weight of composition (C-AAE).

[0037] In some embodiments, the amine is present in the composition (C-AAE) in amounts of about 0.00001 to about 5 wt.-%, preferably from about 0.0001 to about 3 wt.-%, more preferably from about 0.0002 to about 2 wt.-%, still more preferably from about 0.0003 to about 1 wt.-%, such as from about 0.0003 to about 0.5 wt.-%, based on the total weight of composition (C-AAE).

[0038] In some embodiments, the composition (C-AAE) is the crude product of reacting an organic polyol with diketene in the presence of an amine such as a tertiary amine. Suitably, the reaction is conducted in the absence of a solvent. The reaction can be conducted at a temperature of about 10 to about 100 °C, such as of about 20 to about 80 °C, or of about 30 to about 70 °C. Suitable reactions are disclosed in WO 2023 / 094654. The acetoacetate ester (such as one of the at least two different acetoacetate esters) may be any organic compound comprising at least one acetoacetate group linked to the remainder of the compound via an ester. The acetoacetate ester may however also be any organic compound comprising at least two, such as two, three, four, five, six, seven, eight, nine, or ten, acetoacetate groups linked to the remainder of the compound via an ester.

[0039] The acetoacetate ester may also be referred to as (poly)alcohol comprising at least one acetoacetate group.

[0040] In some embodiments, the acetoacetate ester is a polyalcohol comprising at least one acetoacetate group, which is derived from an organic polyol comprising at least 2 hydroxyl groups such as at least 3 hydroxyl groups. In this connection, it is to be understood that in a polyalcohol comprising at least one acetoacetate group that is derived from an organic polyol comprising at least 2 hydroxyl groups, at least one of said at least 2 hydroxyl groups are substituted by the respective acetoacetate group.

[0041] In some embodiments, the organic polyol has from 2 to 10 hydroxyl groups. Preferably, the organic polyol has from 3 to 8 hydroxyl groups, such as from 3 to 7 hydroxyl groups, from 3 to 6 hydroxyl groups, from 3 to 5 hydroxyl groups, or from 3 to 4 hydroxyl groups.

[0042] In some embodiments, the polyalcohol comprising at least one acetoacetate group comprises from 1 to 10 acetoacetate groups, preferably from 2 to 10 acetoacetate groups, more preferably from 3 to 8 acetoacetate groups, such as from 3 to 7 acetoacetate groups, from 3 to 6 acetoacetate groups, from 3 to 5 acetoacetate groups, or from 3 to 4 acetoacetate groups.

[0043] The p-hydroxybutyrate ester (such as the at least two different p-hydroxybutyrate esters) may be any organic compound comprising at least one p-hydroxybutyrate group linked to the remainder of the compound via an ester. The p-hydroxybutyrate ester may however also be any organic compound comprising at least two, such as two, three, four, five, six, seven, eight, nine, or ten, p-hy- droxybutyrate groups linked to the remainder of the compound via an ester.

[0044] The organic polyol according to the present invention comprises 2 or more hydroxyl functional groups.

[0045] In some embodiments, the organic polyol is a linear, branched, or cyclic organic compound with 2 to 18 carbon atoms having at least two hydroxyl groups, preferably at least three hydroxyl groups. In some embodiments, the organic polyol is selected from a linear or branched C2-12 alkyl substituted with at least 2 hydroxyl groups, preferably at least 3 hydroxyl groups, or a C3-8 cycloalkyl substituted with at least 2 hydroxyl groups, preferably at least 3 hydroxyl groups.

[0046] Preferably, the linear or branched C2-12 alkyl substituted with at least 2 hydroxyl groups, preferably at least 3 hydroxyl groups, is selected from the group consisting of glycerol, trimethylolpropane, butanetriol, 2-methyl-propanetriol, pentanetriol, 3-methyl-pentanetriol, hexanetriol, pentaerythritol, butanetetrol, pentanetetrol, hexanetetrol, hexanepentol, and combinations thereof.

[0047] Preferably, the C3-8 cycloalkyl substituted with at least 2 hydroxyl groups, preferably at least 3 hydroxyl groups, is selected from the group consisting of cyclopentanetriol, cyclohexanetriol, cyclopentanetetrol, cyclohexanetetrol, and combinations thereof.

[0048] In some embodiments, the organic polyol is selected from the group consisting of 1 ,4-butanediol, 1 ,6-hexanediol, neopentyl glycol, 4,8-bis(hydroxymethyl)tricyclo[5.2.1 .02,6]decane, 2-methyl-1 ,3 - propanediol, mono-, di-, tri- and tetraethylene glycol, polyethylene glycol, mono-, di-, tri- and tetrapropylene glycol, polypropylene glycol, cyclohexane dimethanol, trimethylolethane, trimethylolpropane, ethoxylated trimethylolethane, propoxylated trimethylolethane, ethoxylated trimethylolpropane, propoxylated trimethylolpropane, pentaerythritol, and glycerol, preferably glycerol.

[0049] In some embodiments, the organic polyol is selected from the group consisting of 1 ,4-butanediol, 1 ,6-hexanediol, neopentyl glycol, 4,8-bis(hydroxymethyl)tricyclo[5.2.1 .02,6]decane, 2-methyl-1 ,3 - propanediol, mono-, di-, tri- and tetraethylene glycol, polyethylene glycol, mono-, di-, tri- and tetrapropylene glycol, polypropylene glycol, cyclohexane dimethanol, trimethylolethane, trimethylolpropane, ethoxylated trimethylolethane, propoxylated trimethylolethane, ethoxylated trimethylolpropane, propoxylated trimethylolpropane, pentaerythritol, and glycerol, more preferably glycerol, and x + y is from 1 to the number of hydroxyl groups of the initial organic polyol A.

[0050] In some embodiments, the organic polyol is selected from the group consisting of monosaccharides, sugar alcohols, and sugar acids.

[0051] Monosaccharides generally have the chemical formula CnH2nOn. Monosaccharides can be classified by the number x of carbon atoms they contain (CH2O)X: trioses (x=3), tetroses (x=4), pentoses (x=5), hexoses (x=6) and heptoses (x=7). In some embodiments, the monosaccharide is selected from tetroses, pentoses, hexoses, heptoses, and combinations thereof. Preferably, the monosaccharide is selected from aldotetroses, ketotetroses, aldopentoses, ketopentoses, aldohexosen, ketohexoses, aldoheptoses, ketoheptoses, and combinations thereof.

[0052] In some embodiments, the monosaccharide is selected from the group consisting of erythrose, thre- ose, erythrulose, ribose, arabinose, xylose, lyxose, desoxyribose, ketopentose, ribulose, xylulose, allose, altrose, glucose, mannose, gulose, idose, galactose, talose, n-acetyl-d-glucosamin, glucosa- min, N-acetyl-D-galactosamin, fucose, rhamnose, chinovose, fructose, 2-desoxy-D-glucose, fluordesoxyglucose, 6-desoxyfructose, 1 ,6-dichlorfructose, 3,6-anhydrogalactose, 1-O-methylgalac- tose, 1-O-methyl-D-glucose, 1-O-methyl-D-fructose, 3-O-methyl-D-fructose, 6-O-methyl-D-galac- tose, sedoheptulose, mannoheptulose, L-glycero-D-manno-heptose, and combinations thereof.

[0053] Sugar alcohols (also called polyhydric alcohols, polyalcohols, alditols or glycitols) are organic compounds, typically derived from sugars, containing one hydroxyl group (-OH) attached to each carbon atom.

[0054] In some embodiments, the sugar alcohol is selected from the group consisting of erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, and combinations thereof.

[0055] A sugar acid is generally a monosaccharide with a carboxyl group at one end or both ends of the carbon chain. Main classes of sugar acids include aldonic acids, ulosonic acids, uronic acids, and aldaric acids. In aldonic acids, the aldehyde group (-CHO) located at the initial end (position 1) of an aldose is oxidized. In ulosonic acids, the -CH2(OH) group at the initial end of a 2-ketose is oxidized yielding an a-ketoacid. In uronic acids, the -CH2(OH) group at the terminal end of an aldose or ketose is oxidized. In aldaric acids, both ends (-CHO and -CH2(OH)) of an aldose are oxidized.

[0056] In some embodiments, the sugar acid is selected from aldonic acids, ulosonic acids, uronic acids, aldaric acids, and combinations thereof. Preferably, the sugar acid is selected from the group consisting of xylonic acid, gluconic acid, ascorbic acid, neuraminic acid, ketodeoxyoctonic acid, glucuronic acid, galacturonic acid, iduronic acid, mucic acid, saccharic acid, and combinations thereof.

[0057] In some embodiments, the organic polyol is selected from the group consisting of glycerol, sorbitol, xylitol, mannitol, erythritol, maltitol, glucose, glucitol, ribulose, pentaerythritol, trimethylolpropane, and combinations thereof. In some embodiments, the at least two different acetoacetate esters differ in the AA amount linked to the remainder of said compounds.

[0058] In some embodiments, the composition (C-AAE) comprises at least two different compounds of formula 1

[0059] 1 wherein

[0060] A is derived from an organic polyol, x is at least 1 , y is 0 or at least 1 , and n is 0 or an integer of 1 to 10.

[0061] In this connection, it is to be understood that the at least two different acetoacetate esters can be e.g. compounds of formula 1.

[0062] Further, it is to be understood that a composition (C-AAE) comprising at least two different compounds of formula 1 comprises at least two compounds of formula 1 as defined herein, wherein these two compounds of formula 1 are different in A, x, y, and / or n, preferably in x and / or y.

[0063] Generally, x + y is from 1 to the number of hydroxyl groups of the initial organic polyol A.

[0064] In some embodiments, one of the at least two different compounds of formula 1 is a compound of formula 1-i, wherein x + y is the number of hydroxyl groups of the initial organic polyol A.

[0065] In this connection, the at least two different p-hydroxybutyrate esters may be compounds of formula 2

[0066]

[0067] 2 wherein

[0068] A is derived from an organic polyol, x is at least 1 , y is 0 or at least 1 , n is 0 or 1 or an integer of 1 to 10, wherein one of the at least two different p-hydroxybutyrate esters of formula 2, is a compound of formula 2-i, wherein x is the number of hydroxyl groups of the initial organic polyol A and y is 0.

[0069] In some embodiments n is 0 such as all n are 0.

[0070] In other embodiments n is 1 such as all n are 1 .

[0071] In some embodiments, A is derived from an organic polyol selected from the group consisting of 1 ,4-butanediol, 1 ,6-hexanediol, neopentyl glycol, 4,8-bis(hydroxymethyl)tricyclo[5.2.1 . 02, 6]decane, 2-methyl-1 ,3 -propanediol, mono-, di-, tri- and tetraethylene glycol, polyethylene glycol, mono-, di-, tri- and tetrapropylene glycol, polypropylene glycol, cyclohexane dimethanol, trimethylolethane, trimethylolpropane, ethoxylated trimethylolethane, propoxylated trimethylolethane, ethoxylated trimethylolpropane, propoxylated trimethylolpropane, pentaerythritol, and glycerol, more preferably glycerol, and x + y is from 1 to the number of hydroxyl groups of the initial organic polyol A.

[0072] In some embodiments, A of the at least two different compounds of formula 1 are the same. In some embodiments, n of the at least two different compounds of formula 1 are the same. In preferred embodiments, A and n of the at least two different compounds of formula 1 are the same.

[0073] In some embodiments, the composition (C-AAE) comprises at least two different compounds of formula 1-2 wherein

[0074] A is derived from an organic polyol, x is an integer of 1 to 6, preferably of 1 to 4, more preferably of 1 to 3, and in particular of 1 to 2 or

[0075] 1 , and y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, preferably wherein one of the at least two different compounds of formula 1-2 is a compound of formula 1-2-i, wherein x + y is the number of hydroxyl groups of the initial organic polyol A.

[0076] In preferred embodiments, A of the at least two different compounds of formula 1-2 are the same.

[0077] In some embodiments, the composition (C-AAE) comprises a compound of formula 1-2-i and at least one compound of formula 1-2-ii

[0078] 1-2-i and 1-2-ii, wherein in the compound of formula 1-2-i

[0079] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A; and wherein in the compound of formula 1-2-ii

[0080] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 1 . The compound of formula 1-2-ii may encompass every suitable AA substitution pattern.

[0081] The compound of formula 1-2-i can be referred to as a fully esterified acetoacetate ester.

[0082] In some embodiments, the composition (C-AAE) further comprises at least one compound of formula 1-2-iii

[0083] 1-2-iii wherein in the compound of formula 1-2-iii

[0084] A is derived from an organic polyol, x is an integer of 1 to 6, preferably of 1 to 5, more preferably of 1 to 4, and in particular of 1 , 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 2.

[0085] The compound of formula 1-2-iii may encompass every suitable AA substitution pattern.

[0086] In some embodiments, A of the compound of formula 1-2-i and the compound of formula 1-2-ii as well as of optional present compound of formula 1-2-iii are the same.

[0087] In some embodiments, A of the compound of formula 1-2-i and the compound of formula 1-2-ii as well as of optional present compound of formula 1-2-iii is glycerol.

[0088] In some embodiment, the composition (C-AAE) comprises the compound of formula 1-2-i in excess. In some embodiments, the composition (C-AAE) comprises at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 80 wt.-%, still more preferably at least about 85 wt.-%, and in particular at least about 86 wt.-%, of the compound of formula 1-2-i, based on the total weight of the composition (C-AAE). In some embodiments, the composition (C-AAE) comprises up to about 89 wt.-% or up to about 90 wt.-%, of the compound of formula 1-2-i, based on the total weight of the composition (C-AAE).

[0089] In some embodiments, the composition (C-AAE) comprises about 60 to about 90 wt.-%, preferably about 70 to about 90 wt.-%, more preferably about 80 to about 90 wt.-%, still more preferably about 85 to about 90 wt.-%, and in particular about 86 to about 89 wt.-%, of a compound of formula 1-2-i, based on the total weight of the composition (C-AAE). In some embodiments, the composition (C-AAE) comprises about 1 to about 30 wt.-%, preferably about 2 to about 25 wt.-%, more preferably about 3 to about 20 wt.-%, still more preferably about 4 to about 15 wt.-%, and in particular about 5 to about 10 wt.-%, of a compound of formula 1-2-ii, based on the total weight of the composition (C-AAE).

[0090] In some embodiments, the compound of formula 1-2-i and the at least one compound of formula 1- 2-ii are present in the composition (C-AAE) in a weight ratio of at least about 2:1 , preferably of at least about 4:1 , more preferably of at least of about 5:1 , still more preferably of at least about 6:1 , and in particular of at least about 7:1. In some embodiments, the compound of formula 1-2-i and the at least one compound of formula 1-2-ii are present in the composition (C-AAE) in a weight ratio of about 2:1 to about 25:1 , preferably of about 3:1 to about 20:1 , more preferably of about 5:1 to about 16:1 , and in particular of about 7:1 to about 13:1 or of about 7:1 to about 8.5:1 .

[0091] In some embodiments, the composition (C-AAE) comprises at least two different compounds of formula 1-4

[0092] 1-4 wherein X1 , X2, and X3 are independently AA (acetoacetate) or OH and wherein one of the at least two different compounds of formula 1-4 is a compound of formula 1-4-i, wherein each X1 , X2, and X3 is AA.

[0093] In some embodiments, the composition (C-AAE) comprises a compound of formula 1-4-i, wherein each X1 , X2, and X3 is AA and at least one compound of formula 1-4-ii, wherein two of X1 , X2, and X3 are AA and the remaining of X1 , X2, and X3 is OH. In this connection, the composition (C-AAE) preferably comprises the compound of formula 1-4-i in excess such as the composition (C-AAE) comprises at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 80 wt.-%, still more preferably at least about 85 wt.-%, and in particular at least about 86 wt.- %, of a compound of formula 1-4-i, based on the total weight of the composition (C-AAE). The compound of formula 1-4-i may be present in the composition (C-AAE) up to about 89 wt.-% or up to about 90 wt.-%, based on the total weight of the composition (C-AAE). A composition (C-AAE) comprising a compound of formula 1-4-i and three different compounds of formula 1-4-ii may be expressed as follows:

[0094] X1'^=AA In some embodiments, the composition (C-BHB) comprises at least two different compounds of formula 2-2

[0095] 2-2.

[0096] In this connection, it is to be understood that the at least two different p-hydroxybuterate esters can be e.g. compounds of formulae 2-2, 2-3(a) / (b), 2-3(a)-i, 2-3(a)-ii, 2-3-iii, 2-4, etc..

[0097] In some embodiments, the composition (C-BHB) comprises at least two different compounds of formula 2-3

[0098] 2-3. In some embodiments, the composition (C-BHB) comprises a compound of formula 2-3-i and at least one compound of formula 2-3-ii

[0099] 2-3-i and 2-3-ii wherein in the compound of formula 2-3-i

[0100] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A; and wherein in the compound of formula 2-3-ii

[0101] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 1 .

[0102] In some embodiments, the composition (C-BHB) further comprises at least one compound of formula 2-3-iii

[0103] 2-3-iii wherein in the compound of formula 2-3-iii

[0104] A is derived from an organic polyol, x is an integer of 1 to 6, preferably of 1 to 5, more preferably of 1 to 4, and in particular of 1 , 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 2.

[0105] In some embodiments, the composition (C-BHB) comprises at least two different compounds of formula 2-3a

[0106] 2-3a. In other embodiments, the composition (C-BHB) comprises at least two different compounds of formula 2-3b

[0107] 2-3b.

[0108] In some embodiments, the composition (C-BHB) comprises a compound of formula 2-3a-i and at least one compound of formula 2-3a-ii

[0109] 2-3a-i and 2-3a-ii wherein in the compound of formula 2-3a-i

[0110] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A; and wherein in the compound of formula 2-3a-ii A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 1 .

[0111] In some embodiments, the composition (C-BHB) comprises the compound of formula 2-3-i such as the compound of formula 2-3a-i, in excess. In some embodiments, the composition (C-BHB) comprises at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.-%, of the compound of formula 2-3-i such as the compound of formula 2-3a-i, based on the total weight of the composition (C-BHB). The compound of formula 2-3-i such as the compound of formula 2-3a-i may be present in the composition (C-BHB) up to about 89 wt.-% or up to about 90 wt.-%, based on the total weight of the composition (C-BHB). In some embodiments, the composition (C-BHB) comprises about 60 to about 90 wt.-%, preferably about 70 to about 90 wt.-%, more preferably about 75 to about 90 wt.-%, still more preferably about 80 to about 90 wt.-%, and in particular about 82 to about 89 wt.-%, of a compound of formula 2-3-i, based on the total weight of the composition (C-BHB).

[0112] In some embodiments, the composition (C-BHB) comprises about 1 to about 30 wt.-%, preferably about 2 to about 25 wt.-%, more preferably about 3 to about 20 wt.-%, still more preferably about 4 to about 15 wt.-%, and in particular about 4 to about 11 wt.-%, of a compound of formula 2-3-ii, based on the total weight of the composition (BHB).

[0113] In some embodiments, the compound of formula 2-3-i and the at least one compound of formula 2- 3-ii are present in the composition (C-BHB) in a weight ratio of at least about 2:1 , preferably of at least about 4:1 , more preferably of at least of about 5:1 , still more preferably of at least about 6:1 , and in particular of at least about 7:1. In some embodiments, the compound of formula 2-3-i and the at least one compound of formula 2-3-ii are present in the composition (C-BHB) in a weight ratio of about 2:1 to about 20:1 , preferably of about 3:1 to about 15:1 , more preferably of about 5:1 to about 12:1 , and in particular of about 7:1 to about 11 :1 or of about 7:1 to about 8.5:1 .

[0114] In some embodiments, the composition (C-BHB) comprises at least two different compounds of formula 2-4

[0115] 2-4 wherein Y1 , Y2, and Y3 are independently BHB (p-hydroxy butyrate) or OH, wherein one of the at least two different compounds of formula 2-4 is a compound of formula 2-4-i, wherein each Y1 , Y2, and Y3 is BHB.

[0116] In some embodiments, the composition (C-BHB) comprises a compound of formula 2-4-i, wherein each Y1 , Y2, and Y3 is BHB and at least one compound of formula 2-4-ii, wherein two of Y1 , Y2, and Y3 are BHB and the remaining of Y1 , Y2, and Y3 is OH. In this connection, the composition (C- BHB) preferably comprises the compound of formula 2-4-i in excess such as the composition (C- BHB) comprises at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.- %, of a compound of formula 2-4-i, based on the total weight of the composition (C-BHB). The compound of formula 2-4-i may be present in the composition (C-BHB) up to about 89 wt.-% or up to about 90 wt.-%, based on the total weight of the composition (C-BHB).

[0117] A composition (C-BHB) comprising a compound of formula 2-4-i and three different compounds of formula 2-4-ii may be expressed as follows: with and

[0118] In some embodiments, the composition (C-BHB) comprises at least two different compounds of formula 2-5

[0119] 2-5 wherein

[0120] A is derived from an organic polyol, x is at least 1 , y is 0 or at least 1 , x + y is from 2 to the number of hydroxyl groups of the initial organic polyol A, and n is 0 or 1 , wherein one of the at least two different p-hydroxybutyrate esters of formula 2-5, is a compound of formula 2-5-i, wherein x is the number of hydroxyl groups of the initial organic polyol A and y is 0.

[0121] In some embodiments, the composition (C-BHB) comprises at least two different compounds of formula 2-6 In some embodiments, the composition (C-BHB) comprises at least two different a compounds of formula 2-6a

[0122] 2-6a, such as at least two different compounds of formula 2-6aa

[0123] 2-6aa.

[0124] In some embodiments, the composition (C-BHB) comprises at least two different compounds of formula 2-6b

[0125] 2-6b such as at least two different compounds of formula 2-6bb

[0126] 2-6 bb In some embodiments, the composition (C-BHB) comprises a mixture of i) one of the above p-hy- droxybuterate ester compounds, wherein x + y is equal to the number of hydroxyl groups of the initial polyol A and ii) at least one of the above p-hydroxybuterate ester compounds, wherein x + y is equal to the number of hydroxyl groups of the initial polyol A minus 1 . Preferably all A are the same such as glycerol. Any suitable hydrogen source may be applied.

[0127] In some embodiments, the hydrogen source is hydrogen gas.

[0128] In some embodiments, the hydrogen source is a monohydric alcohol. Suitable monohydric alcohols are ethanol, propanol, butanol, and pentanol. Monohydric, secondary alcohols are preferred. Preferably, isopropanol is applied. In this connection, the process suitably comprises an alcohol dehydrogenase enzyme that converts the hydroxyl group of said alcohol to the respective keto group. For example, phenylacetaldehyde reductase (PAR) or Leifsonia alcohol dehydrogenase (LSADH) as disclosed in Itoh et al. (Efficient synthesis of optically pure alcohols by asymmetric hydrogen-trans- fer biocatalysis: application of engineered enzymes in a 2-propanol-water medium, Appl Microbiol Biotechnol (2012) 93:1075-1085) may be suitable.

[0129] In some embodiments, the hydrogen source is a monosaccharide. Suitable, the monosaccharide is an aldohexose such as (DZL)-allose, (DZL)-glucose, (DZL)-mannose, (DZL)-galactose, or the like. In this connection, the process suitably comprises the respective dehydrogenase enzyme. For example, D-glucose dehydrogenase (GDH) as disclosed in Zhu et al. (A recombinant ketoreductase toolbox. Assessing the substrate selectivity and stereoselectivity toward the reduction of p-ketoesters, Tetrahedron (2006) 62:901-905) may be suitable.

[0130] In some embodiments, the hydrogen source is adjusted as necessary depending on the desired reduction grade of the product, i.e. depending on how many BHB groups are desired.

[0131] In some embodiments, the molar amount of hydrogen source in the process is of about 1 to about 500 equivalents, preferably of about 1 to about 100 equivalents, more preferably of about 1 to about 10 equivalents, and in particular of about 1 to about 2 equivalents or of about 1 to about 1 .05 equivalents, of the total molar equivalents of acetoacetate groups of the at least two different acetoacetate esters.

[0132] In another embodiments, the molar amount of hydrogen source in the process is of about 0.1 to about 1 equivalents, preferably of about 0.2 to about 0.9 equivalents, more preferably of about 0.3 to about 0.7 equivalents, and in particular of about 0.4 to about 0.6 equivalents, of the total molar equivalents of acetoacetate groups of the at least two different acetoacetate esters.

[0133] In some embodiments, the catalyst is an enzyme. In some embodiments, the enzyme is selected from the group consisting of alcohol dehydrogenase enzyme (e.g. selected from the list consisting of phenylacetaldehyde reductase (PAR), Leifsonia alcohol dehydrogenase (LSADH), and mixtures thereof), ketoreductase enzyme, and mixtures thereof. In this connection, the process is preferably free of metal-based catalysts such as free of Ni-based catalysts, Pd-based catalysts, Pt-based catalysts, Ru-based catalysts, Co-based catalysts, Ir-based catalysts, or Rh-based catalysts.

[0134] In this connection, mixture (M1) may further comprise nicotinamide adenine dinucleotide (NAD+) and / or nicotinamide adenine dinucleotide phosphate (NADP+), preferably in a concentration of about 0.001 to about 100 mM, more preferably of about 0.01 to about 10 mM, still more preferably of about 0.1 to 5 mM or of about 0.5 to about 3 mM.

[0135] In an enzymatic hydrogenation process, the hydrogen source is preferably isopropanol, glucose, or sodium formate.

[0136] Suitably, the enzymatic hydrogenation process is conducted at a pressure of about 0.1 to about 2.0 bar, preferably of about 0.2 to about 1 .7 bar or of about 0.5 to about 1 .5 bar, and in particular of about 0.8 to about 1 .2 bar. An enzymatic hydrogenation process is further suitably conducted at a temperature of about 0 to about 45 °C, preferably of about 20 to about 45 °C, more preferably of about 28 to about 43 °C, still more preferably of about 30 to about 40 °C, and in particular of about 30 to about 35 °C.

[0137] In some embodiments, step a) is performed in the presence of a buffer.

[0138] In some embodiments, the buffer is selected form the group consisting of phosphate buffer such as K2HPO4 / KH2PO4, 4-(2-hydroxyethyl)-1 -piperazineethanesulfonic acid (HEPES) buffer, tris(hy- droxymethyl)aminomethane (TRIS) buffer, 3-(N-morpholino)propanesulfonic acid (MOPS), ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0139] In some embodiments, the buffer is present in mixture (M1) in a concentration of about 0.1 mM to about 1 ,000 mM, preferably of about 1 mM to about 500 mM, more preferably of about 10 mM to about 300 mM. and in particular of about 20 mM to about 250 mM.

[0140] In some embodiments, step a) is conducted at a pH of about 4 to about 9, preferably about 5 to about 8, and in particular about 6 to about 7.

[0141] In some embodiments, step a) is conducted in aqueous medium such as water. In this connection, the starting material (e.g. the at least two different acetoacetate esters) may be dissolved in a suitable solvent such as dimethyl sulfoxide as necessary.

[0142] In some embodiments, the process further comprises additives such as magnesium sulfate. In some embodiments, the catalyst is a metal-based catalyst. In this connection, the hydrogen source is preferably hydrogen gas. In some embodiments, the metal-based catalyst is a Ru-based catalyst. Suitable Ru-based catalysts are heterogeneous Ru-based catalysts such as Ru / C or homogeneous Ru-based catalysts such as a ruthenium complex with mono or diphosphine ligands well known in the chemistry of enantioselective hydrogenations, for example the homogeneous catalyst Ru((R)-BINAP)CI2. Suitably, the Ru-based catalyst is selected from the group consisting of Ru / C, Ru-Macho-BH (carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)amino]ruthe- nium(ll); CAS 1295649-41-0), (R)-RuCI[(p-Cymol)(SEGPHOS®)]CI (Chloro-[(R)-(+)-5,5'-bis-(diphe- nylphosphino)-4,4'-bi-1 ,3-benzodioxol]-(p-cymol)-ruthenium(ll)-chlorid; CAS 944451-28-9), (R)- RuCI[(p-Cymol)(BINAP)]CI (Chloro-[(R)-(+)-2,2'-bis-(diphenylphosphino)-1 ,1 '-binaphthyl]-(p-cymol)- ruthenium(l)-chlorid; CAS 145926-28-9), Ru-Macho® (also known as Carbonylchlorohydrido{bis[2- (diphenylphosphinomethyl)ethyl]amino}ethyl]amino}ruthenium(ll); CAS 1295649-40-9), and mixtures thereof, and in particular Ru / C.

[0143] In some embodiments, the metal-based catalyst is applied in amounts of about 1 to about 12 wt.-%, preferably of about 2 to about 11 wt.-%, more preferably of about 3 to about 10 wt.-%, still more preferably of about 5 to about 9 wt.-%, and in particular of about 6 to about 8 wt.-% such as about 7.5 wt.-%, based on the weight of the composition (C-AAE).

[0144] In some embodiments, the mixture (M1) further comprises an organic solvent.

[0145] Suitable organic solvents are, for example, polar aprotic solvents, typically dimethylformamide, dimethylacetamide, acetonitrile, dimethyl sulfoxide; cyclic or acyclic ethers, typically tetrahydrofuran or dioxane or methyl tert-butyl ether; chlorinated solvents, typically dichloromethane; non-polar aprotic solvents, typically toluene or hexane; polar protic solvents, such as a linear or branched C1- C6 alcohol, in particular methanol, ethanol, isopropanol or butanol; esters, for example ethyl acetate, isopropyl acetate, butyl acetate; or carboxylic acids, for example acetic acid or propionic acid; or water; or mixtures of two or more of said solvents, preferably 2 or 3.

[0146] In some embodiments the solvent is selected from the group consisting of diethyl ether, MTBE, tet- rahydrofurane, n-pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, DMF, acetonitrile, toluene, chloroform, 1 ,4-dioxan, o / m / p-xylene, 2-methyltetrahydrofuran, cyclopentyl methyl ether, alcohols, alkyl alkynates, and mixtures thereof, preferably wherein the organic solvent is selected from the group consisting of acetate esters, propionate esters, diethyl ether, MTBE, tetrahydrofurane, n- pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, acetonitrile, toluene, chloroform, 1 ,4- dioxan, o / m / p-xylene, 2-methyltetrahydrofuran, cyclopentyl methyl ether, methanol, ethanol, propanol, isopropanol, 1 -buntanol, sec-butyl alcohol, isobutanol, and mixtures thereof, more preferably selected from the group consisting of ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, propyl propionate, diethyl ether, MTBE, tetrahydrofurane, n-pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, acetonitrile, toluene, chloroform, 1 ,4-dioxan, o / m / p-xylene, 2-methyltetrahydrofuran, cyclopentyl methyl ether, methanol, ethanol, propanol, isopropanol, 1- buntanol, sec-butyl alcohol, isobutanol, and mixtures thereof, and in particular ethyl acetate.

[0147] In some embodiments, the mixture (M1) further comprises an organic solvent and contacting the mixture (M1) with the hydrogen source, preferably hydrogen gas, in the presence of a metal-based catalyst is conducted at a temperature of about 0 °C to the reflux temperature of the organic solvent. The reflux temperature can be adjusted depending on the applied pressure.

[0148] In some embodiments, the hydrogen source is hydrogen gas and contacting the mixture (M1) with the hydrogen gas in the presence of a catalyst, preferably a metal-based catalyst, is conducted at a temperature of about 0 to about 350 °C, preferably of about 20 to about 250 °C, more preferably of about 30 to about 200 °C, even more preferably of about 30 to about 150 °C, still more preferably of about 50 to about 120 °C, and in particular of about 55 to about 100 °C.

[0149] In some embodiments, step a) is conducted at elevated pressure, preferably at a pressure of about 1 to about 150 bar, more preferably of about 2 to about 100 bar, even more preferably of about 3 to about 50 bar, still more preferably of about 4 to about 20 bar, and in particular of about 6 to about 15 bar.

[0150] In some embodiments, the process further comprises a purifying step b).

[0151] In some embodiments, the process further comprises the step b1) filtering off the catalyst, preferably the metal-based catalyst, providing a mixture (M2a).

[0152] In some embodiments, the process further comprises the step b2) adding to the mixture (M2) / (M2a) activated carbon. The activated carbon can be filtered off and washed with a suitable solvent such as after mixing the activated carbon with the Mixture (M2) / (M2a) for about 0.1 to about 10 hours, or for about 0.2 to about 5 hours, or for about 0.3 to about 3 hours.

[0153] In some embodiments, the process further comprises the step b1) filtering off the catalyst, preferably the metal-based catalyst, providing a mixture (M2a) and the step b2) adding to the mixture (M2a) activated carbon. The activated carbon can sufficiently remove traces of the present amine, as well as of the applied catalyst, preferably of the applied the metal-based catalyst. In some embodiments, the purifying step b) is conducted at a temperature of about to about 0 to about 100 °C, preferably of about 10 to about 50 °C, more preferably of about 15 to about 30 °C such as about 25 °C.

[0154] In some embodiments, the activated carbon is added to the mixture (M2) at a temperature of about to about 0 to about 100 °C, preferably of about 10 to about 50 °C, more preferably of about 15 to about 30 °C such as about 25 °C.

[0155] In some embodiments, the process is conducted batch wise. In some embodiments, the process is a continuous process.

[0156] As indicated above, the present invention relates in a second aspect to a composition (C-BHB) comprising at least two different p-hydroxybutyrate esters of formula 2

[0157] 2 wherein

[0158] A is derived from an organic polyol, x is at least 1 , y is 0 or at least 1 , n is 0 or 1 , wherein one of the at least two different p-hydroxybutyrate esters of formula 2, is a compound of formula 2-i, wherein x is the number of hydroxyl groups of the initial organic polyol A and y is 0.

[0159] In this connection, it is to be understood that a composition (C-BHB) comprising at least two different compounds of formula 2 comprises at least two different compounds of formula 2 as defined herein, wherein these two different compounds of formula 2 are different in A, x, y, and / or n, preferably in x and / or y.

[0160] Particular embodiments as regards p-hydroxybutyrate esters (e.g. compounds of formulae 2-2, 2- 3(a) / (b) 2-3(a)-i, 2-3(a)-ii 2-3-iii , 2-4(-i) / (-ii), 2-5, 2-6(a) / (aa) / (b) / (bb) as well as the respective amounts / ratios), ingredients, moieties, and conditions are already above-outlined in more detail and shall apply for the composition, as well. In the following, certain embodiments of the present invention are described in further details. It is to be understood that each embodiment is relevant on its own as well as in combination with other embodiments.

[0161] In some embodiments, the composition (C-BHB) comprises up to about 90 wt.-% or up to about 89 wt.-% and at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.-%, of the compound of formula 2-i, based on the total weight of the composition (C-BHB).

[0162] In some embodiments, the composition (C-BHB) comprises a compound of formula 2-3-i and at least one compound of formula 2-3-ii

[0163] 2-3-i and 2-3-ii wherein in the compound of formula 2-3-i

[0164] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A; and wherein in the compound of formula 2-3-ii

[0165] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 1 .

[0166] In preferred embodiments, all A are the same such as glycerol.

[0167] In some embodiments, the composition (C-BHB) comprises the compound of formula 2-3-i such as the compound of formula 2-3a-i, in excess. In some embodiments, the composition (C-BHB) comprises at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.-%, of the compound of formula 2-3-i such as the compound of formula 2-3a-i, based on the total weight of the composition (C-BHB). The compound of formula 2-3-i such as the compound of formula 2-3a-i may be present in the composition (C-BHB) up to about 89 wt.-% or up to about 90 wt.-%, based on the total weight of the composition (C-BHB).

[0168] In some embodiments, the composition (C-BHB) comprises about 60 to about 90 wt.-%, preferably about 70 to about 90 wt.-%, more preferably about 75 to about 90 wt.-%, still more preferably about 80 to about 90 wt.-%, and in particular about 82 to about 89 wt.-%, of a compound of formula 2-3-i, based on the total weight of the composition (C-BHB).

[0169] In some embodiments, the composition (C-BHB) comprises about 1 to about 30 wt.-%, preferably about 2 to about 25 wt.-%, more preferably about 3 to about 20 wt.-%, still more preferably about 4 to about 15 wt.-%, and in particular about 4 to about 11 wt.-%, of a compound of formula 2-3-ii, based on the total weight of the composition (BHB).

[0170] In some embodiments, the compound of formula 2-3-i and the at least one compound of formula 2- 3-ii are present in the composition (C-BHB) in a weight ratio of at least about 2:1 , preferably of at least about 4:1 , more preferably of at least of about 5:1 , still more preferably of at least about 6:1 , and in particular of at least about 7:1. In some embodiments, the compound of formula 2-3-i and the at least one compound of formula 2-3-ii are present in the composition (C-BHB) in a weight ratio of about 2:1 to about 20:1 , preferably of about 3:1 to about 15:1 , more preferably of about 5:1 to about 12:1 , and in particular of about 7:1 to about 11 :1 or of about 7:1 to about 8.5:1 .

[0171] In some embodiments, the composition (C-BHB) comprises at least one compound of formula 2-4

[0172] 2-4 wherein Y1 , Y2, and Y3 are independently BHB (p-hydroxy butyrate) or OH and wherein one of the at least two different compounds of formula 2-4 is a compound of formula 2-4-i, wherein each Y1 , Y2, and Y3 is BHB.

[0173] In some embodiments, the composition (C-BHB) comprises a compound of formula 2-4-i, wherein each Y1 , Y2, and Y3 is BHB and at least one compound of formula 2-4-ii, wherein two of Y1 , Y2, and Y3 are BHB and the remaining of Y1 , Y2, and Y3 is OH. In this connection, the composition (C- BHB) preferably comprises the compound of formula 2-4-i in excess such as the composition (C- BHB) comprises at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.- %, of a compound of formula 2-4-i, based on the total weight of the composition (C-BHB). The compound of formula 2-4-i may be present in the composition (C-BHB) up to about 89 wt.-% or up to about 90 wt.-%, based on the total weight of the composition (C-BHB).

[0174] In some embodiments, the composition (C-BHB) is obtained by a process according to the first aspect, preferably after the purifying step b), such as filtering off the catalyst, preferably the metalbased catalyst, providing a mixture (M2a) and / or adding to the mixture (M2) / (M2a) activated carbon.

[0175] As indicated above, the present invention relates in a third aspect to the use of activated carbon to purify a mixture comprising a composition (C-BHB) comprising at least two different p-hydroxybutyr- ate esters and an amine, and optionally a catalyst, preferably a metal-based catalyst, wherein one of the at least two different p-hydroxybutyrate esters does not comprise a hydroxyl group.

[0176] Particular embodiments as regards p-hydroxybutyrate esters (e.g. compounds of formulae 2-2, 2- 3(a) / (b), 2-3(a)-i, 2-3(a)-ii, 2-3-iii, 2-4(-i) / (-ii), 2-5, 2-6(a) / (aa) / (b) / (bb) as well as the respective amounts / ratios), ingredients and moieties are already above-outlined in more detail and shall apply for the use, as well. In the following, certain embodiments of the present invention are described in further details. It is to be understood that each embodiment is relevant on its own as well as in combination with other embodiments.

[0177] In some embodiments, the composition (C-BHB) comprises at least one compound, preferably at least two different compounds, of formula 2

[0178] 2 wherein

[0179] A is derived from an organic polyol, x is at least 1 , y is 0 or at least 1 , n is 0 or 1 , wherein one of the at least two different p-hydroxybutyrate esters of formula 2, is a compound of formula 2-i, wherein x is the number of hydroxyl groups of the initial organic polyol A and y is 0.

[0180] In this connection, it is to be understood that the at least two different p-hydroxybutyrate esters can be expressed as a compound of e.g. formula 2 and the like.

[0181] In some embodiments, the composition (C-BHB) comprises up to about 90 wt.-% or up to about 89 wt.-% and at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.-%, of the compound of formula 2-i, based on the total weight of the composition (C-BHB).

[0182] In some embodiments, the composition (C-BHB) comprises a compound of formula 2-3-i and at least one compound of formula 2-3-ii

[0183] 2-3-i and 2-3-ii wherein in the compound of formula 2-3-i

[0184] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A; and wherein in the compound of formula 2-3-ii

[0185] A is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 1 .

[0186] In some embodiments, the composition (C-BHB) further comprises at least one compound of formula 2-3-iii 2-3-iii wherein in the compound of formula 2-3-iii

[0187] A is derived from an organic polyol, x is an integer of 1 to 6, preferably of 1 to 5, more preferably of 1 to 4, and in particular of 1 , 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 2.

[0188] In some embodiments, the composition (C-BHB) comprises the compound of formula 2-3-i such as the compound of formula 2-3a-i, in excess. In some embodiments, the composition (C-BHB) comprises at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.-%, of the compound of formula 1-2-i such as the compound of formula 2-3a-i, based on the total weight of the composition (C-BHB). The compound of formula 2-3-i such as the compound of formula 2-3a-i may be present in the composition (C-BHB) up to about 89 wt.-% or up to about 90 wt.-%, based on the total weight of the composition (C-BHB).

[0189] In some embodiments, the composition (C-BHB) comprises at least one of compound of formula 2- 4

[0190] 2-4 wherein Y1 , Y2, and Y3 are independently BHB (p-hydroxy butyrate) or OH and wherein one of the at least two different compounds of formula 2-4 is a compound of formula 2-4-i, wherein each Y1 , Y2, and Y3 is BHB.

[0191] In some embodiments, the composition (C-BHB) comprises a compound of formula 2-4-i, wherein each Y1 , Y2, and Y3 is BHB and at least one compound of formula 2-4-ii, wherein two of Y1 , Y2, and Y3 are BHB and the remaining of Y1 , Y2, and Y3 is OH. In this connection, the composition (C- BHB) preferably comprises the compound of formula 2-4-i in excess such as the composition (C- BHB) comprises at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.- %, of a compound of formula 2-4-i, based on the total weight of the composition (C-BHB). The compound of formula 2-4-i may be present in the composition (C-BHB) up to about 89 wt.-% or up to about 90 wt.-%, based on the total weight of the composition (C-BHB).

[0192] A composition (C-BHB) comprising a compound of formula 2-4-i and three different compounds of formula 2-4-ii may be expressed as follows: with and

[0193] In some embodiments, the catalyst is a metal-based catalyst, preferably is a Ru-based catalyst, more preferably a Ru-based catalyst selected from the group consisting of Ru / C, Ru-Macho-BH (carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)amino]ruthenium(ll); CAS 1295649-41-0), (R)-RuCI[(p-Cymol)(SEGPHOS®)]CI (Chloro-[(R)-(+)-5,5'-bis-(diphenylphosphino)- 4,4'— bi— 1 ,3-benzodioxol]-(p-cymol)-ruthenium(ll)-chlorid; CAS 944451-28-9), (R)-RuCI[(p-Cy- mol)(BINAP)]CI (Chloro-[(R)-(+)-2,2'-bis-(diphenylphosphino)-1 ,1 '-binaphthyl]-(p-cymol)-ruthe- nium(l)-chlorid; CAS 145926-28-9), Ru-Macho® (also known as Carbonylchlorohydrido{bis[2-(di- phenylphosphinomethyl)ethyl]amino}ethyl]amino}ruthenium(ll); CAS 1295649-40-9), and mixtures thereof, and in particular Ru / C.

[0194] In some embodiments, the amine is a tertiary amine, preferably selected from the group consisting of trimethylamine, trimethylamine (TEA), tripropylamine, 1 ,1 ,3,3-tetramethylguanidine (TMG), 1 ,4- diazabicyclo[2.2.2]octane (DABCO), N,N-dimethylisopropylamine, 1 ,8-Diazabicyclo(5.4.0)undec-7- ene (DBU), 1 ,5-Diazabicyclo(4.3.0)non-5-ene (DBN), and mixtures thereof, and in particular 1 ,4-di- azabicyclo[2.2.2]octane (DABCO).

[0195] In some embodiments, In some embodiments, the mixture further comprises an organic solvent.

[0196] In some embodiments the solvent is selected from the group consisting of diethyl ether, MTBE, tet- rahydrofurane, n-pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, DMF, acetonitrile, toluene, chloroform, 1 ,4-dioxan, o / m / p-xylene, 2-methyltetrahydrofuran, cyclopentyl methyl ether, alcohols, alkyl alkynates, and mixtures thereof, preferably wherein the organic solvent is selected from the group consisting of acetate esters, propionate esters, diethyl ether, MTBE, tetrahydrofurane, n- pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, acetonitrile, toluene, chloroform, 1 ,4- dioxan, o / m / p-xylene, 2-methyltetrahydrofuran, cyclopentyl methyl ether, methanol, ethanol, propanol, isopropanol, 1 -buntanol, sec-butyl alcohol, isobutanol, and mixtures thereof, more preferably selected from the group consisting of ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, propyl propionate, diethyl ether, MTBE, tetrahydrofurane, n-pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, acetonitrile, toluene, chloroform, 1 ,4-dioxan, o / m / p-xylene, 2-methyltetrahydrofuran, cyclopentyl methyl ether, methanol, ethanol, propanol, isopropanol, 1- buntanol, sec-butyl alcohol, isobutanol, and mixtures thereof, and in particular ethyl acetate.

[0197] In some embodiments, the activated carbon is added to the mixture at a temperature of about to about 0 to about 100 °C, preferably of about 10 to about 50 °C, more preferably of about 15 to about 30 °C such as about 25 °C.

[0198] In some embodiments, the mixture is the mixture (M2) or of (M2a).

[0199] In some embodiments, the activated carbon has a total surface area (B.E.T.) of about 500 to about 4000 m2 / g, preferably of about 800 to about 3000 m2 / g, more preferably of about 1000 to about 2500 m2 / g, and in particular of about 1200 to about 2000 m2 / g.

[0200] It will be obvious for a person skilled in the art that these embodiments and items only depict examples of a plurality of possibilities. Hence, the embodiments shown here should not be understood to form a limitation of these features and configurations. Any possible combination and configuration of the described features can be chosen according to the scope of the invention.

[0201] Examples

[0202] Hydrogenation of AAGIy mixture

[0203] First Step: Esterification

[0204] In a reactor glycerol (1 eq.) and DABCO (0.0013 eq.) were mixed and heated to 40 °C. Diketene (2.97 eq.) was added within 20.5 hours at 40 °C to the reaction mixture. After dosing, the reaction mixture was heated for further 1 hours at 50 °C. An AA-Glycerol (AA-Gly) mixture comprising about 87 wt.-% of triple AA-Gly and about 7 wt.-% of double AA-Gly was obtained as a highly viscous orange resin (=99 %).

[0205] Second Step: Hydrogenation 70 C, 8 h

[0206] AAGIy BHB-Glycerol mixture

[0207] X-j2 3—AA Y1 2 3=BHB

[0208] X-!2=AA; X3=OH Y.,2=BHB; Y3=OH

[0209] X-, 3=AA; X2=OH Y-I3=BHB; Y2=OH

[0210] X2 3=AA; X- OH Y2 3=BHB; Y^OH

[0211] In an autoclave, AA-Gly (1 eq.), ethyl acetate (5.4 eq.) and Ru / C (5% Ru, wet, 6.0 wt%) were mixed. The reactor was charged with hydrogen (10 bar) and heated to 70 °C. The hydrogenation was stopped after 8 hours. The reaction mixture was cooled to room temperature and the catalyst was filtered off. The reaction mixture was mixed with charcoal (activated charcoal, 20 wt%) and mixed for 1 hour at room temperature. The charcoal was filtered off and the charcoal was washed with ethyl acetate. A BHB-Glycerol mixture comprising about 85 wt.-% of triple BHB-Gly and about 8 wt.-% of double BHB-Gly (=90%) was obtained as a slightly yellowish resin after distillation.

Claims

Claims1 . A process for reducing at least two different acetoacetate esters comprising the step of a) contacting a mixture (M1) comprising a composition (C-AAE) comprising the at least two different acetoacetate esters with a hydrogen source in the presence of a catalyst to obtain a mixture (M2) comprising a composition (C-BHB) comprising at least two different p-hydroxybutyrate ester, wherein the mixture (M1) comprises an amine and wherein one of the at least two different acetoacetate esters does not comprise a hydroxyl group.

2. The process according claim 1 , wherein the amine is a tertiary amine, preferably selected from the group consisting of trimethylamine, trimethylamine (TEA), tripropylamine, 1 ,1 ,3, 3-tetra- methylguanidine (TMG), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), N,N-dimethylisopropylamine, 1 ,8- Diazabicyclo(5.4.0)undec-7-ene (DBU), 1 ,5-Diazabicyclo(4.3.0)non-5-ene (DBN), and mixtures thereof, and in particular 1 ,4-diazabicyclo[2.2.2]octane (DABCO), and / or wherein the amine is present in the composition (C-AAE) in amounts of about 0.00001 to about 5 wt.-%, preferably from about 0.0001 to about 3 wt.-%, more preferably from about 0.0002 to about 2 wt.-%, still more preferably from about 0.0003 to about 1 wt.-%, such as from about 0.0003 to about 0.5 wt.-%, based on the total weight of composition (C-AAE).

3. The process according to claim 1 or 2, wherein the hydrogen source is hydrogen gas or selected from the group consisting of isopropanol, glucose, and sodium formate.

4. The process according to any one of claims 1 to 3, wherein the composition (C-AAE) comprises at least two different compounds of formula 11 whereinA is derived from an organic polyol, x is at least 1 ,y is 0 or at least 1 , and n is 0 or an integer of 1 to 10, preferably wherein one of the at least two different compounds of formula 1 is a compound of formula 1-i, wherein x + y is the number of hydroxyl groups of the initial organic polyol A.

5. The process according to claim 4, whereinA and / or n of the at least two different compounds of formula 1 are the same, preferably wherein A and n of the at least two different compounds of formula 1 are the same; and / or whereinA is derived from an organic polyol selected from the group consisting of 1 ,4-butanediol, 1 ,6-hex- anediol, neopentyl glycol, 4,8-bis(hydroxymethyl)tricyclo[5.2.1 . 02, 6]decane, 2-methyl-1 ,3 -propanediol, mono-, di-, tri- and tetraethylene glycol, polyethylene glycol, mono-, di-, tri- and tetrapropylene glycol, polypropylene glycol, cyclohexane dimethanol, trimethylolethane, trimethylolpropane, ethoxylated trimethylolethane, propoxylated trimethylolethane, ethoxylated trimethylolpropane, propoxylated trimethylolpropane, pentaerythritol, and glycerol, more preferably glycerol, and x + y is from 1 to the number of hydroxyl groups of the initial organic polyol A.

6. The process according to any one of claims 1 to 5, wherein the composition (C-AAE) comprises at least two different compounds of formula 1-21-2, whereinA is derived from an organic polyol, x is an integer of 1 to 6, preferably of 1 to 4, more preferably of 1 to 3, and in particular of 1 to 2 or1 , and y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2.

7. The process according to claim 6, wherein the composition (C-AAE) comprises a compound of formula 1-2-i and at least one compound of formula 1-2-ii1-2-i and 1-2-ii, wherein in the compound of formula 1-2-iA is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A; and wherein in the compound of formula 1-2-iiA is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 1 , preferably wherein A of the compound of formula 1-2-i and the compound of formula 1-2-ii are the same.

8. The process according to claim 7, wherein the composition (C-AAE) comprises up to about 90 wt.-%, and at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 80 wt.-%, still more preferably at least about 85 wt.-%, and in particular at least about 86 wt.- %, of a compound of formula 1-2-i, based on the total weight of the composition (C-AAE).

9. The process according to any one of claims 4 to 8, wherein each A is glycerol.

10. The process according to any one of claims 1 to 9, wherein the catalyst is a metal-based catalyst, preferably wherein the metal-based catalyst is a Ru-based catalyst, more preferably a Ru- based catalyst selected from the group consisting of Ru / C, Ru-Macho-BH (carbonylhydrido(tetrahy- droborato)[bis(2-diphenylphosphinoethyl)amino]ruthenium(ll); CAS 1295649-41-0), (R)-RuCI[(p-Cymol)(SEGPHOS®)]CI (Chloro-[(R)-(+)-5,5'-bis-(diphenylphosphino)-4,4'— bi— 1 ,3-benzodioxol]-(p-cymol)-ruthenium(ll)-chlorid; CAS 944451-28-9), (R)-RuCI[(p-Cy- mol)(BINAP)]CI (Chloro-[(R)-(+)-2,2'-bis-(diphenylphosphino)-1 ,1'-binaphthyl]-(p-cymol)-ruthe- nium(l)-chlorid; CAS 145926-28-9), Ru-Macho® (also known as Carbonylchlorohydrido{bis[2-(di- phenylphosphinomethyl)ethyl]amino}ethyl]amino}ruthenium(ll); CAS 1295649-40-9), and mixtures thereof, and in particular Ru / C, and / orwherein the catalyst is a metal-based catalyst and is applied in amounts of about 1 to about 12 wt.- %, preferably of about 2 to about 11 wt.-%, more preferably of about 3 to about 10 wt.-%, still more preferably of about 5 to about 9 wt.-%, and in particular of about 6 to about 8 wt.-%, based on the weight of the composition (C-AAE).

11. The process according to any one of claim 1 to 10, wherein the mixture (M1) further comprises an organic solvent such as diethyl ether, MTBE, tetrahydrofurane, n-pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, DMF, acetonitrile, toluene, chloroform, 1 ,4-dioxan, o / m / p-xy- lene, 2-methyltetrahydrofuran, cyclopentyl methyl ether, alcohols, alkyl alkynates, and mixtures thereof, preferably wherein the organic solvent is selected from the group consisting of acetate esters, propionate esters, diethyl ether, MTBE, tetrahydrofurane, n-pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, acetonitrile, toluene, chloroform, 1 ,4-dioxan, o / m / p-xylene, 2-methyltetra- hydrofuran, cyclopentyl methyl ether, methanol, ethanol, propanol, isopropanol, 1 -buntanol, sec-bu- tyl alcohol, isobutanol, and mixtures thereof, more preferably selected from the group consisting of ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, propyl propionate, diethyl ether, MTBE, tetrahydrofurane, n-pentane, cyclopentane, n-hexane, cyclohexane, n-hep- tane, acetonitrile, toluene, chloroform, 1 ,4-dioxan, o / m / p-xylene, 2-methyltetrahydrofuran, cyclopentyl methyl ether, methanol, ethanol, propanol, isopropanol, 1 -buntanol, sec-butyl alcohol, isobutanol, and mixtures thereof, and in particular ethyl acetate.

12. The process according to any one of claims 1 to 11 , the hydrogen source is hydrogen gas and wherein contacting the mixture (M1) with the hydrogen gas in the presence of a catalyst, preferably a metal-based catalyst, is conducted at a temperature of about 0 to about 350 °C, preferably of about 20 to about 250 °C, more preferably of about 30 to about 200 °C, even more preferably of about 30 to about 150 °C, still more preferably of about 50 to about 120 °C, and in particular of about 55 to about 100 °C, and / or wherein step a) is conducted at elevated pressure, preferably at a pressure of about 1 to about 150 bar, more preferably of about 2 to about 100 bar, even more preferably of about 3 to about 50 bar, still more preferably of about 4 to about 20 bar, and in particular of about 6 to about 15 bar.

13. The process according to any one of claims 1 to 12, further comprising the step b1) filtering off the catalyst, preferably the metal-based catalyst, providing a mixture (M2a) and / or the step b2) adding to the mixture (M2) / (M2a) activated carbon.

14. A composition (C-BHB) comprising at least two different p-hydroxybutyrate esters of formula 2whereinA is derived from an organic polyol, x is at least 1 , y is 0 or at least 1 , n is 0 or 1 , wherein one of the at least two different p-hydroxybutyrate esters of formula 2, is a compound of formula 2-i, wherein x is the number of hydroxyl groups of the initial organic polyol A and y is 0.

15. The composition (C-BHB) according to claim 14, comprising a compound of formula 2-3-i and at least one compound of formula 2-3-ii2-3-i and 2-3-ii wherein in the compound of formula 2-3-iA is derived from an organic polyol other than glycerol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A; and wherein in the compound of formula 2-3-iiA is derived from an organic polyol other than glycerol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 1 , preferably wherein all A are the same.

16. The composition (C-BHB) according to claim 14 or 15, comprising the compound of formula 2-i, preferably the compound of formula 2-3-i, in excess, preferably wherein the composition (C- BHB) comprises up to about 90 wt.-% and at least about 60 wt.-%, preferably at least about 70 wt.- %, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.-%, of the compound of formula 2-i, preferably the compound of formula 2-3-i, based on the total weight of the composition (C-BHB).

17. Use of activated carbon to purify a mixture comprising a composition (C-BHB) comprising at least two different p-hydroxybutyrate esters and an amine and optionally a catalyst, preferably a metal-based catalyst, wherein one of the at least two different p-hydroxybutyrate esters does not comprise a hydroxyl group.

18. The use according to claim 17, wherein the composition (C-BHB) comprises at least two different compounds of formula 22 whereinA is derived from an organic polyol, x is at least 1 , y is 0 or at least 1 , n is 0 or 1 , wherein one of the at least two different p-hydroxybutyrate esters of formula 2, is a compound of formula 2-i, wherein x is the number of hydroxyl groups of the initial organic polyol A and y is 0, preferably wherein the composition (C-BHB) comprises up to about 90 wt.-% and at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.-%, of the compound of formula 2-i, based on the total weight of the composition (C-BHB).

19. The use according to claim 17 or 18, wherein the catalyst is a metal-based catalyst, which is a Ru-based catalyst, preferably a Ru-based catalyst selected from the group consisting of Ru / C,Ru-Macho-BH (carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)amino]ruthe- nium(ll); CAS 1295649-41-0), (R)-RuCI[(p-Cymol)(SEGPHOS®)]CI (Chloro-[(R)-(+)-5,5'-bis-(diphe- nylphosphino)-4,4'-bi-1 ,3-benzodioxol]-(p-cymol)-ruthenium(ll)-chlorid; CAS 944451-28-9), (R)- RuCI[(p-Cymol)(BINAP)]CI (Chloro-[(R)-(+)-2,2'-bis-(diphenylphosphino)-1 ,1'-binaphthyl]-(p-cymol)- ruthenium(l)-chlorid; CAS 145926-28-9), Ru-Macho® (also known as Carbonylchlorohydrido{bis[2- (diphenylphosphinomethyl)ethyl]amino}ethyl]amino}ruthenium(ll); CAS 1295649-40-9), and mixtures thereof, and in particular Ru / C; and / or the amine is a tertiary amine, preferably selected from the group consisting of trimethylamine, trimethylamine (TEA), tripropylamine, 1 ,1 ,3, 3-tetramethylguanidine (TMG), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), N,N-dimethylisopropylamine, 1 ,8-Diazabicyclo(5.4.0)undec-7-ene (DBU), 1 ,5-Diazabicy- clo(4.3.0)non-5-ene (DBN), and mixtures thereof, and in particular 1 ,4-diazabicyclo[2.2.2]octane (DABCO).

20. The composition (C-BHB) according to claim 14, comprising a compound of formula 2-3-i and at least one compound of formula 2-3-ii2-3-i and 2-3-ii wherein in the compound of formula 2-3-iA is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A; and wherein in the compound of formula 2-3-iiA is derived from an organic polyol, x is an integer of 2 to 6, preferably of 2 to 5, more preferably of 2 to 4, and in particular of 2 or 3, y is 0 or at least 1 , preferably 0 or an integer of 1 to 4, more preferably 0 or an integer of 1 to 3, and in particular 0 or an integer of 1 to 2, and x + y is the number of hydroxyl groups of the initial organic polyol A minus 1 , preferably wherein all A are the same; the composition further comprising the compound of formula 2-i, preferably the compound of formula 2-3-i, in excess, preferably wherein the composition (C-BHB) comprises up to about 90 wt. %and at least about 60 wt.-%, preferably at least about 70 wt.-%, more preferably at least about 75 wt.-%, still more preferably at least about 80 wt.-%, and in particular at least about 82 wt.-%, of the compound of formula 2-i, preferably the compound of formula 2-3-i, based on the total weight of the composition (C-BHB).

Images