Resolution of 4-cyano-4-(4-nitrophenyl)hexanoic acid: Synthesis of (R) and (S)-3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione (aminoglutethimide1)

✍ Scribed by Osman Achmatowicz; Iwona Malinowska; Barbara Szechner; Jan K. Maurin

• Book ID: 104207845
• Publisher: Elsevier Science
• Year: 1997
• Tongue: French
• Weight: 641 KB
• Volume: 53
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(97)00464-x

✦ Synopsis

Using (R)-or (S)-l-phenylethylamine as a resolving agent, (R)-and (S)-4-cyano-4-(4nitrophenyl)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 aminoghitethimide. Attempted resolution of the other precursor of aminoghtethimide, 4-cyano-2-ethyl-(4-nitrophenyl)butanoic acid with (S)-l-phenylethylamine led to the formation of the double salt. Its crystal structure was elucidated by X-ray crystallographic analysis.