Preparation of optical isomers of 3-methylfentanyl derivatives as analgesics.

Abstract

Title compds. I (R1 = F, Cl, NO2, NH2, etc; CR2R3 = CHOH, CO) are synthesized by adding 2-(4-R1-phenyl)oxirane with 3-methyl-4-phenylaminopiperidine in or without aprotic solvent (such as toluene, chloroform, dichloromethane, etc), acylating with propanoyl chloride or propanoic anhydride in aprotic solvent, and hydrolyzing with K2CO3 in water-methanol. Cis-(+)-(3R,4S,2'S)-I (R1 = F, CR2R3 = CHOH) was prepd. and had an analgesic ED50 of 0.774 μg/kg s.c. vs. an ED50 of 13.9 mg/kg for morphine in the hot plate test using mice. [on SciFinder(R)]