http://rdf.ncbi.nlm.nih.gov/pubchem/patent/RU-2544859-C1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_b593b0ca3affc17217f7f3209292cc29 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07B57-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07C227-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07C227-34 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07C229-08 |
| filingDate | 2013-12-20-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| grantDate | 2015-03-20-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_515202eac6351e8c77f9a92235fa243b http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_d739e1b0263470890f0da36f2644737a http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_9a49ce7cb3376a5777fce3bc54ec9366 |
| publicationDate | 2015-03-20-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | RU-2544859-C1 |
| titleOfInvention | Method of producing (s)-3-aminomethyl-5-methylhexanoic acid (pregabalin) |
| abstract | FIELD: chemistry.SUBSTANCE: invention relates to a method of producing (S)-(+)-3-aminomethyl-5-methylhexanoic acid (pregabalin) of formula (I)The method includes steps (a)-(g). Step (a) includes reacting alkyl ether of cyanoacetic acid CNCHCOOR (A) and isobutyraldehyde to obtain alkyl ether of 2-cyano-4-methylpentanoic acid (B)At step (b) the obtained ether (B) reacts with ethyl ether of alpha-haloacetic acid (Hal=Cl, Br, I) in the presence of a base at 10-90°C in a solvent, such as N,N-dimethyl formamide, tetrahydrofuran, 1,4-dioxane, diemthyl sulphoxide and dimethoxyethane, or without a sovent to form 4-ethyl-1-methyl-2-cyano-2-isobutylsuccinate (C)Step (c) includes hydrolysis of compound (C) under the action of a base, such as an alkali metal hydroxide, at 20-80°C, to obtain 2-cyano-2-isobutylsuccinic acid. Step (d) includes decarboxylation of the obtained 2-cyano-2-isobutylsuccinic acid in the presence of a mineral acid, e.g. sulphuric or hydrochloric acid, in an organic solvent, e.g. ethyl acetate, at 70-80°C to obtain (RS)-3-cyano-5-methylhexanoic acid. Step (e) includes separating enantiomers of the obtained (RS)-3-cyano-5-methylhexanoic acid by forming a corresponding salt with cinchonidine in an organic solvent, such as ethanol, methanol, 1,4-dioxane, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, dimethoxyethane and diethylene glycol dimethyl ether, at 20-80°C, separating the cinchonidine salt of (S)-3-cyano-5-methylhexanoic acid and additional purification thereof by repeated salt formation in ethyl acetate. At step (f) the cinchonidine salt of (S)-3-cyano-5-methylhexanoic acid is treated with a mixture of ethyl acetate and diluted hydrochloric acid (1:1) at room temperature and the (S)-3-cyano-5-methylhexanoic acid (II)formed is separated from the organic layer. Step (g) includes hydrogenation of the separated optically pure (S)-3-cyano-5-methylhexanoic acid (II), which is catalysed by Raney nickel, to form (S)-(+)-3-aminomethyl-5-methylhexanoic acid (pregabalin) (I). The method is characterised by that at step (a) reaction of the alkyl ether of cyanoacetic acid CNCHCOOR, where R=C-C-alkyl, with isobutyraldehyde is carried out under the action of carbon monoxide at pressure of 1-200 atm and temperature of 20-200°C in a polar solvent, such as methanol, ethanol, water, 1,4-dioxane, tetrahydrofuran, acetonitrile, dimethoxyethane and diethylene glycol dimethyl ether, and the catalyst used is a cobalt, nickel, ruthenium or rhodium compound; at step (b) the base used is sodium hydride.EFFECT: method reduces the number of steps when producing an intermediate, reduces the amount of wastes and improves environmental safety.5 ex |
| priorityDate | 2013-12-20-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 139.