RESOLUTION OF 4 CYANO-4-(4-NITROPHENYL)HEXANOIC ACID - SYNTHESIS OF (R) AND (S)-3-(4-AMINOPHENYL)-3-ETHYLPIPERIDINE-2,6-DIONE (AMINOGLUTETHIMIDE)

摘要

Using (R)- or (S)-1-phenylethylamine as a resolving agent, (R)- and (S)-4-cyano-4-(4-nitrophenyl)hexanoic acids have been isolated. Cyclization of each enantiomer, followed by reduction of the nitro group, afforded (R)- and (S)-aminoglutethimide of high (>99% ee) enantiomeric purity, respectively. The absolute configuration of (R)-(+)-3-(4-nitrophenyl)-3-ethylpiperidine-2, 6-dione was solved by X-ray single crystal analysis thus establishing the (R)-configuration of the dextrorotatory aminoglutethimide. Attempted resolution of the other precursor of aminoglutethimide, 4cyano-2-ethyl(4-nitrophenyl)butanoic acid with (S)-1-phenylethylamine led to the formation of the double salt. Its crystal structure was elucidated by X-ray crystallographic analysis. (C) 1997 Elsevier Science Ltd. [References: 16]