Conversion of L-pyroglutamic acid to 4-alkyl-substituted L-prolines. The synthesis of trans-4-cyclohexyl-L-proline

• Published in: Journal of organic chemistry Vol. 51; no. 16; pp. 3140 - 3143
• Main Authors: Thottathil, John K, Moniot, Jerome L, Mueller, Richard H, Wong, Michael K. Y, Kissick, Thomas P
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.08.1986; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Five membered ring; Aminoalcohol; Condensation reaction; Epimerization; Lithium Tetrahydroaluminates; Nitrogen heterocycle; Lactam; Chemical reduction; Stereoselectivity; Hydrochlorides; Aminoacid; Trans stereoisomer; Ethylenic compound
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00366a011

(S)-5-(Hydroxymethyl)-2-pyrrolidinone (3), prepared from L-pyroglutamic acid, was condensed with benzaldehyde to obtain the O,N-acetal 4 in excellent yield. Alkylation of 4 with 3-bromocyclohexene followed by reduction gave trans-4-cyclohexyl-L-prolinol (7) in good chemical yield with excellent stereoselectivity. Sequential N-protection, oxidation of the alcohol to the acid, and N-deprotection furnished trans-4-cyclohexyl-L-proline (1) in excellent yield and quality. Compound 1 serves as an intermediate for the preparation of ACE inhibitors including Fosenopril.