RESOLUTION OF ALPHA-(4-FLUOROPHENYL)-4-(5-FLUORO-2-PYRIMIDINYL)-1-PIPERAZINE-BUTANOL (BMS-181100) AND ALPHA-(3-CHLOROPROPYL)-4-FLUOROBENZENEMETHANOL USING LIPASE-CATALYZED ACETYLATION OR HYDROLYSIS

alpha-(3-Chloropropyl)-4-fluorobenzenemethanol, a possible intermediate for synthesis of a potential anti-psychotic agent alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMS 181100), was resolved by acetylation using isopropenyl acetate and lipase PS-30 in heptane. S-alcohol...

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Bibliographic Details
Published inTetrahedron: asymmetry Vol. 5; no. 10; pp. 1925 - 1934
Main Authors HANSON, RL, BANERJEE, A, COMEZOGLU, FT, MIRFAKHRAE, KD, PATEL, RN, SZARKA, LJ
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier 01.10.1994
Subjects
Chemistry
Chemistry, Inorganic & Nuclear
Chemistry, Organic
Chemistry, Physical
Physical Sciences
Science & Technology
ORGANIC-SOLVENTS
INVERSION
ENZYME ENANTIOSELECTIVITY
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Summary:alpha-(3-Chloropropyl)-4-fluorobenzenemethanol, a possible intermediate for synthesis of a potential anti-psychotic agent alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMS 181100), was resolved by acetylation using isopropenyl acetate and lipase PS-30 in heptane. S-alcohol was obtained in 42% yield with >99% optical purity. R-acetate was obtained with 92.6% optical purity by stopping the reaction after 46% conversion. The enzymatically produced acetate was hydrolyzed by lipase PS-30 to give R-alcohol with >99% optical purity after 62-72% conversion. BMS 181100 acetate ester was treated with lipase GC-20 in buffer containing 10% toluene to give the R-alcohol with 97.9% optical purity after 47.6% conversion. The rate and enantioselectivity of hydrolysis by lipase GC-20 were very dependent on the organic solvent. E values ranged from 1 in the absence of organic solvent to >100 with dichloromethane and toluene.
ISSN:0957-4166
DOI:10.1016/S0957-4166(00)86268-0