# US 5,702,928 A · Process for producing optically active triazole compounds and method of racemizing optically active triazole compounds > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,702,928 A - Document ID: US5702928A - Status: Granted - Kind: A - Application number: 08/617,747 - Filed: 1996-05-28 - Granted: 1997-12-30 - Earliest claimed: 1994-07-18 - Assignees: Daicel Chemical Industries, Ltd. - Inventors: Naoki Kawada; Noritsugu Yamazaki; Takafumi Imoto; Kiyoshi Ikura - Web page: https://patentgrep.com/patent/US5702928A ## CPC - C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms - C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms - C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles - C12P 17/10: Nitrogen as only ring hetero atom - C12P 41/004: {by esterification of alcohol- or thiol groups in the enantiomers or the inverse reaction} - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)} ## Abstract A process for the asymmetric synthesis of a compound represented by general formula (II-R) easily at a low cost by using a lipase, and a process for producing a compound to be utilized in the above synthesis. ##STR1## ## Claims ### Claim 1 A process for producing a compound having the formula (II-R), said process comprising the steps of (a) providing a compound having the formula (II), a compound having the formula R.sub.1 COOR.sub.2, and a microbial lipase; and (b) enzymatically reacting said compound having the formula (II) with said compound having the formula R.sub.1 COOR.sub.2, in the presence of said microbial lipase, under conditions permitting formation of a compound having the formula (II-R); ##STR6## wherein X and Y are either halogen or hydrogen atoms, wherein X and Y may be the same or different atoms; wherein the configuration of the asymmetric carbon is R; and wherein R.sub.1 is a straight or branched C.sub.1 to C.sub.4 alkyl or alkenyl group, and R.sub.2 is a straight or branched C.sub.1 to C.sub.6 alkyl or alkenyl group. ### Claim 2 (depends on 1) The process according to claim 1, wherein said lipase is derived from a microorganism belonging to the genus Mucor, Candida, Penicillium, Pseudomonas or Rhizopus. ### Claim 3 (depends on 1) The process according to claim 1, wherein said lipase is derived from Pseudomonas sp FERMP-12575. ### Claim 4 A process for producing a compound having the formula (I-R), said process comprising the steps of (a) providing a compound having the formula (II), a compound having the formula R.sub.1 COOR.sub.2, and a microbial lipase; and (b) enzymatically reacting said compound having the formula (II) with said compound having the formula R.sub.1 COOR.sub.2, in the presence of said microbial lipase, under conditions permitting formation of a compound having the formula (I-R); ##STR7## wherein X and Y are halogen or hydrogen atoms; wherein X and Y may be the same or different atoms; wherein the configuration of the asymmetric carbon is R; and wherein R.sub.1 is a straight or branched C.sub.1 to C.sub.4 alkyl or alkenyl group, R.sub.2 is a straight or branched C.sub.1 to C.sub.6 alkyl or alkenyl group, and R is COR.sub.1. ### Claim 5 (depends on 4) The process according to claim 4, wherein said lipase is derived from microorganism belonging to the genus Geotricum. ### Claim 6 A process for producing a compound having the formula (II-R), said process comprising the steps of (a) providing a compound having the formula (I) and a microbial lipase; and (b) hydrolyzing said compound having the formula (I) in the presence of said microbial lipase, under conditions permitting formation of a compound having the formula (II-R); ##STR8## wherein X and Y are halogen or hydrogen atoms; wherein X and Y may be the same or different atoms; wherein the configuration of the asymmetric carbon is R; and wherein R is COR.sub.1, wherein R.sub.1 is a straight or branched C.sub.1 to C.sub.4 alkyl or alkenyl group. ### Claim 7 (depends on 6) The process according to claim 6, wherein said lipase is derived from a microorganism belonging to the genus Penicillium or Candida. ### Claim 8 A process for producing a compound having the formula (I-R), said process comprising the steps of (a) providing a compound having the formula (I) and a microbial lipase; and (b) hydrolyzing said compound having the formula (I) in the presence of said microbial lipase, under conditions permitting formation of a compound having the formula (I-R); ##STR9## wherein X and Y are halogen or hydrogen atoms; wherein X and Y may be the same or different atoms; wherein the configuration of the asymmetric carbon is R; and wherein R is COR.sub.1, wherein R.sub.1 is a straight or branched C.sub.1 to C.sub.4 alkyl or alkenyl group. ### Claim 9 (depends on 8) The process according to claim 8, wherein said lipase is derived from a microorganism belonging to the genus Mucor, Penicillium, Chromobacterium, Rhizopus, Pseudomonas or Alcaligenes. ### Claim 10 (depends on 1, 4, 6, 8) The process according to claims 1, 4, 6 or 8, wherein both X and Y are fluorine atoms. ### Claim 11 (depends on 1, 4, 6, 8) The process according to claims 1, 4, 6 or 8, wherein R.sub.1 is methyl group. ### Claim 12 (depends on 1, 4) The process according to any one of claims 1 or 4, wherein R.sub.2 is a vinyl group. ### Claim 13 (depends on 1, 4, 6, 8) The process according to claims 1, 4, 6 or 8, wherein both X and Y are fluorine atoms, and where R.sub.1 is methyl group. ### Claim 14 (depends on 1, 4) The process according to claims 1 or 4, wherein both X and Y are fluorine atoms, where R.sub.1 is methyl group, where R.sub.2 is vinyl group. ### Claim 15 (depends on 1) The process according to claim 1, wherein lipase is derived from microorganism belonging to the genus Mucor, Candida, Penicillium, Pseudomonas or Rhizopus, or animals, where both X and Y are fluorine atoms, where R1 is methyl group. ### Claim 16 (depends on 1) The process according to claim 1, wherein lipase is derived from microorganism belonging to the genus Mucor, Candid, Penicillium, Pseudomonas or Rhizopus, or animals, where both X and Y are fluorine atoms, where R.sub.1 is methyl group, where R.sub.2 is vinyl group. ### Claim 17 (depends on 4) The process according to claim 4, wherein lipase is derived from microorganism belonging to genus Geotrichum, where both X and Y are fluorine atoms, where R.sub.1 is methyl group. ### Claim 18 (depends on 9) The process according to claim 9, wherein lipase is derived from microorganism belonging to genus Geotrichum, where both X and Y are fluorine atoms, where R.sub.1 is methyl group, where R.sub.2 is vinyl group. ### Claim 19 (depends on 6) The process according to claim 6, wherein lipase is derived from microorganism belonging to the genus Pencillium or Candid, where both X and Y are fluorine atoms, where R.sub.1 is methyl group. ### Claim 20 (depends on 8) The process according to claim 8, wherein lipase is derived from microorganism belonging to the genus Mucor, Penicillium, Chromobacterium, Rhizopus, Pseudomonas, or Alcaligenes, where both X and Y are fluorine, where R.sub.1 is methyl group. ### Claim 21 A process for producing a compound having the formula (II) comprising reducing or eliminating the optical activity of a compound having the formula (I-R) or (I-S) by treatment with a strong acid followed by deacylation; ##STR10## wherein X and Y are halogen or hydrogen atoms; wherein X and Y may be the same or different atoms; and wherein R is COR.sub.1, wherein R.sub.1 is a hydrogen atom, or a straight or branched alkyl, alkenyl, aryl or aralkyl groups. ### Claim 22 (depends on 21) The process according to claim 21 wherein R.sub.1 is hydrogen atom, or straight or branched alkyl group. ### Claim 23 (depends on 22) The process according to any one of claim 22, wherein R.sub.1 is a methyl group. ### Claim 24 (depends on 21, 22, 23) The process according to claims 21 to 23, wherein both X and Y are fluorine atoms. ### Claim 25 (depends on 21) The process according to claim 21, wherein the reaction is performed in the presence of an acylating agent. ### Claim 26 A process for producing a compound having the formula (II) comprising reducing or eliminating the optical activity of a compound having the formula (II-R) or (II-S) by treatment with a strong acid in the presence of an acylating agent followed by deacylation; ##STR11## wherein X and Y are halogen or hydrogen atoms; wherein X and Y may be the same or different atoms. ### Claim 27 (depends on 26) The process according to claim 26, wherein both X and Y are fluorine atoms. ### Claim 28 (depends on 26, 27) The process according to claims 26 or 27, wherein said acylating agent is aliphatic carboxylic acid. ### Claim 29 (depends on 28) The process according to claim 28, wherein said acylating agent is acetic acid. ### Claim 30 (depends on 28) The process according to claim 28, wherein said acylating agent is formic acid. ### Claim 31 (depends on 21, 22, 23, 25, 26, 27, 29, 30) The process according to any one of claims 21-23, 25-27, 29 or 30, wherein said strong acid is sulfuric acid.