178 results about "Metaclazepam" patented technology

The invention relates to the technical field of hydraulic fracturing exploitation of deep / ultra-deep oil and gas reservoirs, and discloses a gel-coated temporary plugging agent and a preparation method and application thereof.The gel-coated temporary plugging agent comprises a proppant inner core and a degradable gel shell coating the outer surface of the proppant inner core; the degradable gel shell is formed by a gel shell gelling solution, the gel shell gelling solution comprises small-molecule comonomers and a degradable cross-linking agent, and the small-molecule comonomers comprise acrylamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide the initiator is one or more of N, N-dimethylacrylamide, acrylic acid, hydroxyethyl acrylate, benzyl acrylate, 2-propyl acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid and N-vinyl pyrrolidone; and the initiator is one or more of N, N-dimethylacrylamide, acrylic acid, hydroxyethyl acrylate, benzyl acrylate, 2-propyl acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid and N-vinyl pyrrolidone. The gel-coated temporary plugging agent can be used for effectively plugging in a fracturing time period at high temperature / ultrahigh temperature, and the flow conductivity of fractured cracks can be enhanced by exposing an internal propping agent after the gel-coated temporary plugging agent is degraded.

The invention discloses a 5-bromoindole-2-carboxylic acid methyl ester derivative as well as a preparation method and application thereof in a protein inhibitor, and relates to the technical field of synthesis and preparation of inhibitors. According to the 5-bromoindole-2-carboxylic acid methyl ester derivative, compared with a contrast product, the synthetic route steps of the prepared 5-bromoindole-2-carboxylic acid methyl ester derivative are simpler and more convenient, structural modification and preparation are easier, the application range of a substrate is widened, the yield of the product is increased, and the yield of the product is increased. The differentiated requirements on the molecular structure novelty in the field of kinase inhibitors can be met. An epidermal growth factor receptor (EGFR) inhibitor prepared from the 5-bromoindole-2-carboxylic acid methyl ester derivative is higher in inhibition efficiency on biological activity, the physiological solubility is improved more remarkably, a more excellent and stable target binding result can be shown, and the EGFR inhibitor can be used for preparing an epidermal growth factor receptor (EGFR) inhibitor. The application effect of the compound in scenes such as antitumor drug development and the like is favorably improved.

The present application relates to a kind of chalcone amide alpha-glucosidase inhibitors and its preparation and application, the inhibitor structural formula is: preparation method specifically is (1) after 2-hydroxyacetophenone, sodium hydroxide and methyl p-formylbenzoate are reacted, intermediate in formula (a) is obtained after post-processing;(2) intermediate in formula (a) is dissolved in organic solvent and potassium hydroxide is reacted, after reaction, intermediate in formula (b) is obtained after post-processing;(3) intermediate in formula (b) and substituted aniline are dissolved in organic solvent, after reaction, the inhibitor shown in formula (c) is obtained after post-processing.Compared with prior art, the compound of the present application is novel, and experiments show that it has good alpha-glucosidase inhibitory activity, and can be used for preparing alpha-glucosidase activity inhibiting drug.

The invention discloses a phenoxazine skeleton-containing drug small molecule and application thereof, and belongs to the technical field of synthesis of heterocyclic compounds and antitumor drugs, the phenoxazine skeleton-containing drug small molecule has an inhibition effect on HepG2 and A549, a phenoxazine derivative 7c with the third site connected with a methoxy group at the tail end of a phenoxazine structure benzene ring has a better overall effect, and the phenoxazine skeleton-containing drug small molecule can be applied to preparation of antitumor drugs. The inhibition rates of the compound on HepG2 and A549 are respectively 87.67% and 94.23%. 7g of the phenoxazine derivative of which the methyl ester structure is connected to the third site of the phenoxazine structure only has an obvious effect on A549, and the inhibition rate in A549 cells is 96.00%.

The invention discloses a preparation method and application of a compound with a cold sensing regulation effect, which comprises the following steps: dissolving tryptophan in methanol, adding concentrated sulfuric acid, esterifying the acid to protect carboxyl so as to obtain tryptophan methyl ester, dissolving the obtained tryptophan methyl ester and aromatic carboxylic acid substances in N, N-dimethylformamide, and reacting to obtain the compound with the cold sensing regulation effect. The method comprises the following steps: catalyzing 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethylurea hexafluorophosphate and N, N-diisopropylethylamine, dissolving a catalyzed product in ethanol (98%), adding into a NaOH solution, stirring, carrying out rotary evaporation treatment, slowly dropwise adding a 0.5 mol / L hydrochloric acid solution, adjusting the pH value of a reaction system to 3-4, and finally obtaining the tryptophan derivative compound with the yield of 70%. The invention provides a potential medicine for improving the working ability and cold injury in the cold environment for people living and working in the cold environment, and is developed into a medicine for effectively improving neuropathic pain diseases in the cold environment.

The invention discloses a synthesis method of a Vinetoram key intermediate and Vinetoram, and relates to the technical field of organic synthesis.The synthesis method comprises the steps that 1-((4 '-chloro-5, 5-dimethyl-3, 4, 5, 6-tetrahydro-[1, 1'-biphenyl]-2-yl) methyl) piperazine hydrochloride and 2-((1H-pyrrolo [2, 3-b] pyridine-5-yl) oxy)-4-bromobenzoic acid methyl ester are used as reaction raw materials, a reaction is carried out, and the Vinetoram key intermediate and the synthesis method of the Vinetoram key intermediate are synthesized; the method comprises the following steps: carrying out a substitution reaction and a hydrolysis reaction to obtain a key intermediate of the Venotocork, and carrying out a condensation reaction on the intermediate and 3-nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) benzenesulfonamide to obtain the Venotocork. The synthesis method has the advantages of short process route, easily available raw materials, mild reaction conditions, high yield and purity of the intermediate and the Vinetoram, facilitation of the improvement of the yield and quality of the Vinetoram, and reduction of the production cost of the Vinetoram.

The utility model discloses a production system of 1-cyclopropyl-3-(2-methylthio-4-trifluoromethylphenyl) propyl-1, 3-diketone, which comprises an esterification unit and a condensation unit, and is characterized in that the esterification unit is connected with the condensation unit; the production system has the advantages that the production system is simple in connection structure and easy to implement, methyl 2-methylthio-4-trifluoromethyl benzoate is prepared from 2-methylthio-4-trifluoromethyl benzoic acid and the like through an esterification unit and then reacts with cyclopropyl ketone and other raw materials to prepare 1-cyclopropyl-3-(2-(methylthio)-4-(trifluoromethyl) phenyl) propyl-1, 3-diketone, and the production system has the advantages that the production system is simple in connection structure and easy to implement. The generation of three wastes is reduced, and the production cost is reduced; moreover, in the reaction process, the reaction temperature is not high, the reaction condition is mild, the yield is high, the production cost is low, the content of impurities in the product 1-cyclopropyl-3-(2-(methylthio)-4-(trifluoromethyl) phenyl) propyl-1, 3-diketone can be reduced, a high-quality reaction raw material is provided for subsequent industrial production of isoxaflutole, and the method is suitable for large-scale industrial production.

The invention belongs to the technical field of medicines, and particularly relates to a beta-elemene tryptophan methyl ester derivative and application thereof in preparation of antitumor drugs. According to the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I), on the basis of maintaining a beta-elemene structural framework, a tryptophan methyl ester group is introduced to the 13th site of beta-elemene, and unsubstituted C3-7 heterocycloalkyl, substituted C3-7 heterocycloalkyl, unsubstituted C5-11 hetero-spirocycloalkyl or substituted C5-11 hetero-spirocycloalkyl is introduced to the 14th site of beta-elemene, so that the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I) is obtained. The water solubility and the pharmacokinetic property of the compound are effectively improved. Experimental results show that the anti-tumor activity of the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I) provided by the invention is obviously enhanced compared with that of beta-elemene. Formula (I).

The invention belongs to the field of Velciguat synthesis, and particularly relates to a preparation method of Velciguat and an intermediate product thereof. The preparation method of the Velciguat comprises the following steps: (1) reacting aminomalononitrile with methyl chloroformate to generate an intermediate product I; (2) carrying out ring closing on the intermediate product I and formamidine under an alkaline condition to obtain an intermediate product II; (3) carrying out bromination reaction on the intermediate product II and N-bromosuccinimide to obtain an intermediate product III; (4) reacting the intermediate product III with bis (pinacolato) diboron under the action of a catalyst to obtain an intermediate product IV; and (5) carrying out a reaction on the intermediate product IV and 5-fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo [3, 4-b] pyridine to prepare the viriciguat. The method is simple to operate, low in cost and safe in production. The invention also provides the intermediate product obtained by the preparation method.

The invention belongs to the technical field of compound preparation, and particularly provides a preparation method of L-glutamic acid-1-tert-butyl ester, which comprises the following steps: step S1, carrying out imidization reaction on an L-glutamic acid-5-methyl ester compound and benzophenone imine to generate N-dibenzylidene-L-glutamic acid-5-methyl ester; step S2, enabling the N-dibenzylidene-L-glutamic acid-5-methyl ester and tertiary butyl-2, 2, 2-trichloroacetic acid imine ester to be subjected to a tert-butyl esterification reaction, so as to generate N-dibenzylidene-L-glutamic acid-5-methyl ester-1-tert-butyl ester, and enabling the N-dibenzylidene-L-glutamic acid-5-methyl ester-1-tert-butyl ester to be subjected to a tert-butyl esterification reaction; and S3, carrying out hydrolysis reaction on the N-dibenzylidene-L-glutamic acid-5-methyl ester-1-tert-butyl ester to remove a methyl ester group, and removing a protecting group on an amino group, so as to generate the L-glutamic acid-1-tert-butyl ester. The preparation method disclosed by the embodiment of the invention is used for preparing the L-glutamic acid-5-methyl ester-1-tert-butyl ester from the N-dibenzylidene-L-glutamic acid-5-methyl ester-1-tert-butyl ester. According to the application, the tertiary butyl-2, 2, 2-trichloroacetic acid imine ester is used for carrying out the tert-butyl esterification reaction, so that the yield is high, the reaction condition is mild, the post-treatment is simple, the control on the generation of glutamic acid, pyroglutamic acid and pyroglutamic acid tert-butyl ester is facilitated, and the impurities are few.

The invention provides a synthesis method of a medical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine, which comprises the following steps: step S1, trans-4-hydroxy-D-proline methyl ester hydrochloride is used as a raw material, under the action of triethylamine, a reaction is carried out for 2-4 hours, and the reaction product is subjected to post-treatment to obtain the (3R, 5R)-3-Boc-amino-5-fluoropiperidine. Dichloromethane is used as a solvent to react with triphenylchloromethane to obtain (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester; s2, the (4S)-4-hydroxy-1-(triphenyl methyl)-D-proline methyl ester is subjected to oxidation, and 4-oxy-1-(triphenyl methyl)-D-proline methyl ester is obtained; s3, enabling the compound 4-oxo-1-(triphenyl methyl)-D-proline methyl ester to react with hydroxylamine hydrochloride, so as to obtain a compound hydroxylamino-1-(triphenyl methyl)-D-proline methyl ester; step S9, the compound (3R, 5R)-3-Boc amino-1-triphenyl-5-fluoropiperidine is subjected to Trt removal under the action of hydrochloric acid, and a compound (3R, 5R)-3-Boc amino-5-fluoropiperidine is obtained; according to the method disclosed by the invention, the (3R, 5R)-3-Boc amino-5-fluoropiperidine can be efficiently and economically synthesized by optimizing a reaction route.

The application relates to a preparation method of a benzylamine compound and belongs to the field of organic synthesis. The preparation method of the benzylamine compound is as follows: a reaction formula is shown in the description. The application also provides a preparation method of the compound of the above formula (VI). Compared with methyl o-bromomethylbenzoate used in the prior art, methyl o-chloromethylbenzoate used in the application is cheaper, has lower preparation cost, less pollution and is more environment-friendly. Compared with the prior art, the benzylization reaction of the application has higher reaction conversion rate, less dibenzyl impurities, is convenient for product post-treatment and purification, has higher yield, and has better product quality.

Fungicidal compositions comprising carboxamides The present invention relates to fungicidal compositions comprising at least one compound selected from the group consisting (I-1) N-[1,3-dimethyl-1-(phenylmethyl)butyl]-8-fluoro-3- quinolinecarboxamide, (I-2) N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3- carboxamide, (I-3) N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide, as active component 2) at least one compound, or an N-oxide, or an agriculturally useful salt thereof, selected from the group consisting of (II-1) methyl 2-[2-chloro-4-(4- chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate, (II-2) fluoxytioconazole, (II-3) flumetylsulfurim, (II-4) pyrapropoyne, wherein the weight ratio of compound I to compound II is from 10:1 to 1:10. The invention also relates to an agrochemical composition comprising the composition and a solvent of solid carrier. Further, the invention relates to a non-therapeutic use of the inventive compositions controlling phytopathogenic harmful fungi.

The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a benzofuran compound. In an inert gas environment, a 2-fluorotoluene compound as shown in a formula 1 and a methyl benzoate compound as shown in a formula 2 are mixed and reacted with an organic solvent methyl tert-butyl ether in the presence of bis (trimethylsilyl) amino cesium and cesium sulfate, and the benzofuran compound as shown in a formula 3 is synthesized under a heating condition. Wherein the methyl benzoate compound as shown in the formula 2 can also be replaced by 2-naphthoic acid methyl ester or 1-naphthoic acid methyl ester. The research develops a benzofuran synthesis strategy without transition metal catalysis. According to the method, on the basis of commercially available raw materials, the construction of a benzofuran skeleton is realized through a simple and efficient path. Due to the mild and green reaction characteristic, a route with practical value is provided for synthesis of active medicine molecules and key intermediates of the active medicine molecules.

An agent containing at least one aroma compound selected from the group consisting of E-beta-damascone, S-(2-methyl-3-furyl)ethanethioate, beta-caryophyllene oxide, beta-ionone, 2,5-dihydroxy-1,4-dithiane, methyl anthranilate, S-furfuryl thioformate, 1-isothiocyanate-3-(methylthio)propane, nootkatone, 1,4-dioxacycloheptadecane-5,17-dione, sclareol, and sclareolide is effective for masking an unpleasant smell and for making oral products in which an unpleasant smell is masked.

This invention provides an birepiperazole oral solution, wherein the solution comprises birepiperazole 0.4-0.6 mg / ml, disodium edetate 0.1-0.5 mg / ml, methylparaben 1.5-2.0 mg / ml, propylparaben 0.15-0.25 mg / ml, an acidic pH adjuster 2.5-3.5 mg / ml, a flavoring agent 0.8-1.2 mg / ml, propylene glycol 40-60 mg / ml, glycerin 120-180 mg / ml, and a sodium hydroxide solution to adjust the pH to 2.9-3.3. The drug exhibits high stability during preparation, storage, and clinical formulation.

Methods for preparing an L-6-hydroxytryptophan (HTP) derivative and intermediates thereof are provided. The methods for preparing the various intermediates of the L-6-HTP derivative are provided, on the basis of which the L-6-HTP derivative could be obtained. Specifically, the L-6-HTP derivative is obtained by using a compound A6-0 with a structure shown in Formula 1 as a starting reaction raw material, and subjecting the compound A6-0 to triisopropylsilyl (TIPS) protection, coupling, carbon-boron bond oxidation, hydroxyl-targeted benzyl protection, TIPS protective group removal, tert-butoxycarbonyl (Boc) protective group removal, methyl ester hydrolysis, and amino-targeted 9-fluorenylmethoxycarbonyl (Fmoc) protection in sequence.

Described herein are processes for the synthesis of P2X3 antagonists, wherein the P2X3 antagonist is methyl (S)-2-((2-(2,6-difluoro-4-(methylcarbamoyl)phenyl)-7-methylimidazo[1,2-a]pyridin-3-yl)methyl)morpholine-4-carboxylate (Compound 1), or a pharmaceutically acceptable salt or co-crystal thereof.

The invention provides application of mycophenolic acid methyl ester in preparation of antithrombotic drugs, and belongs to the technical field of antithrombotic drugs. The antithrombotic activity of the compound mycophenolic acid methyl ester is found for the first time, and experimental support and theoretical basis are provided for developing novel drugs for treating or preventing thrombus.

The application discloses a stable isoniazid oral solution, which comprises isoniazid, hydroxybenzyl methyl ester, hydroxybenzyl propyl ester, a pH regulator and a solvent. The application prepares the isoniazid oral solution with good stability, improves the absorption and utilization rate of the medicament, and has good taste and market prospect.

Described herein are two processes for the preparation of methyl (5)-2-((2-(2,6-difLuoro-4-(methylcarbamol)phenyl)-7-methylimidaz[1,2-a]pyridine-3-yl)methyl)morpholine-4-carboxylate, a P2X3 antagonist, in a stepwise manner and chemical intermediates used in the synthetic processes.

Methods for the synthesis of a tricyclic-prostaglandin D2 metabolite methyl ester or a pharmaceutically acceptable salt thereof.

A composition comprising (a) a therapeutic agent or a pharmaceutically acceptable salt thereof; (b) a PEG-monoorthoester-lipid; (c) an amphiphilic lipid; (d) a cationic lipid and / or a beta-alanyl-prolyl-cysteine methyl ester; and optionally (e) a steroid and / or a ceramide and / or DOPE. The composition for use as a medicament.

The present invention relates to a method for efficiently producing a compound derived from the commercially available and readily available 3-((3S)-7-bromo-2-((2-hydroxypropyl)amino)-5-(pyridin-2-yl)-3H-benzo[e][1,4]diazepine-3-yl)propionate methyl ester, namely, the compound 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-4-yl]propionate methyl ester benzenesulfonate (remimazolam besylate).

The invention discloses a continuous synthesis method of 1-(2-chlorphenyl)-2-(2-tetrazolyl) ethanone, which comprises the following steps: (1) introducing a trimethylsilylated diazomethane solution and a strong alkali solution into a micro-channel reactor 1 for reaction, introducing the obtained intermediate reaction solution and a 2-chloromethyl benzoate solution into a micro-channel reactor 2 for continuous reaction, the preparation method comprises the following steps: adding 2-chlorophenyl to generate 1-(2-chlorophenyl)-2-(2-tetrazolyl-trimethylsilane) ethanone; and (2) removing a TMS group from the 1-(2-chlorphenyl)-2-(2-tetrazolyl-trimethylsilane) ethanone, and then carrying out post-treatment to obtain the 1-(2-chlorphenyl)-2-(2-tetrazolyl) ethanone. The continuous synthesis method uses a fluid process, has the advantages of small amplification effect, high production efficiency and environmental protection, improves the selectivity of 2-tetrazole, and avoids partial sensitization of intermediates.

The application belongs to the field of chemical industry, and particularly relates to a synthesis method of a substituted pyrazoloquinazoline derivative. The method provided by the application comprises sequentially preparing 2-chloro-5,6,7,8-tetrahydroquinazoline, 2-chloro-6,7-dihydroquinazolin-8(5H)-ketoxime, 2-chloro-6,7-dihydroquinazolin-8(5H)-ketone, 2-(2-methoxy-8-oxo-5,6,7,8-tetrahydroquinazolin-7-yl)-2-oxoacetic acid methyl ester and 1-(2-hydroxyethyl)-8-methoxy-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methyl ester, and finally obtaining 1-(2-hydroxyethyl)-8-((5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide. By using the method of the application, three reaction steps are reduced, the total yield is increased by nearly one time, and the method is far higher than the original process route; and the application of dangerous reagents such as hydrazine hydrate and iodine is avoided, and the method is easy to scale up.

The invention discloses a formaldehyde probe as well as a preparation method and application thereof, and belongs to the technical field of fluorescent probe preparation. Dissolving benzylamine and potassium carbonate in anhydrous acetonitrile, adding 2-bromo-2-methyl propionate, and reacting to obtain a compound 3; dissolving the compound 3 and lithium hydroxide in a mixed solution of tetrahydrofuran and water, reacting for a period of time, and quenching the reaction with hydrochloric acid to obtain a carboxylic acid intermediate 4; and dissolving the carboxylic acid intermediate 4 in dichloromethane, then adding CDM, EDCI and DMAP, and carrying out a reaction to obtain the target product DPM. The DPM is a formaldehyde regeneration type fluorescent probe and can realize formaldehyde detection in a mode of disturbing an endogenous steady state to the minimum extent. The DPM is a steady-state maintenance type formaldehyde probe successfully applied to a spinal cord injury (SCI) model for the first time, and can realize visual monitoring on formaldehyde rise of a diseased region based on a non-invasive living imaging system (IVIS).

The invention relates to a preparation method of a photo-crosslinking agent compound (N-(19-(3-(butyl-3-alkyn-1-yl)-3H-diazacyclopropane-3-yl)-4, 16-dioxo-7, 10, 13-trioxo-3, 17-diazacylalkyl)-4-(7-oxo-7H-furan [3, 2-g] benzopyran-9-yl) oxy) butyramide), which comprises the following steps: by taking xanthoxyl as a starting material, reacting at the temperature of 60-80 DEG C for 1-2 hours, and then adding a catalyst, thereby obtaining the photo-crosslinking agent compound. The method comprises the following steps: sequentially carrying out condensation with fragments such as methyl 4-chlorobutyrate, BOC-ethylenediamine, polyoxydipropionic acid and diaziridine, so as to obtain a high-purity compound with a photo-crosslinking probe effect. The preparation method provided by the invention has the advantages of mild and controllable reaction conditions, high yield and no column chromatography purification operation in post-treatment purification, and is suitable for industrial large-scale production.

The invention discloses a 5-hydroxypyrazole compound as well as a synthesis method and application thereof, and the structural formula of the 5-hydroxypyrazole compound is as follows: 3-phenoxyphenyl-3-oxo-methyl propionate derivative is used as a starting material, the starting material and benzyl bromide derivative are subjected to hydrocarbylation reaction firstly, then the starting material and hydrazine hydrate are subjected to Knorr reaction, and the 5-hydroxypyrazole compound is obtained. Finally, the 5-hydroxy-3-phenoxyphenyl pyrazole ring compound is prepared, and the prepared 5-hydroxypyrazole ring compound shows that the 5-hydroxypyrazole ring compound has a good inhibition effect on HepG2 cells and can be used for further preparing anti-cancer drugs.

The present invention belongs to the technical field of drug synthesis, and particularly relates to a method for preparing a high-purity butrol lithium complex. The preparation method of the present invention comprises the following steps: (1) 9-fluorenone and trimethyl orthoformate are activated by iron p-toluenesulfonate to obtain a ketal, the ketal and cis-1,4-diol are exchanged to obtain a cyclic ketal, and the cyclic ketal is oxidized to obtain an epoxy side chain 3,5,8-trioxaspiro[bicyclo[5.1.0]octane-4,9'-fluorene]; (2) cyclocyclohexane and 3,5,8-trioxaspiro[bicyclo[5.1.0]octane-4,9'-fluorene] are subjected to an epoxy ring-opening reaction in an organic solvent under the action of a lithium salt to generate an intermediate I; (3) the intermediate I and an α-substituted acetate are subjected to nitrogen alkylation in an organic solvent to generate an intermediate II; (4) the ester group of the intermediate II is hydrolyzed under alkaline conditions to obtain an intermediate III; and (5) the ketal is removed from the intermediate III under acidic conditions to obtain a butrol lithium complex.