AN EFFICIENT SYNTHESIS OF METHYL N-[2-(R)-(1-NAPHTHYLMETHYL)-3-(MORPHOLINOCARBONYL)PROPIONYL]-(S)-HISTIDINATE, THE KEY SYNTHETIC INTERMEDIATE OF RENIN INHIBITORS

Optically pure (R)-(1-naphthylmethyl)succinic acid could be efficiently prepared by a combination of optical resolution and racemization of the undesired enantiomer or by catalytic asymmetric reduction of (1-naphthylmethylene)succinic acid over a rhodium (I)-chiral phosphine complex. Highly chemoselective amide formation of di-4-nitrophenyl (R)-(1-naphthylmethyl)succinate with morpholine followed by coupling with methyl (S)-histidinate readily produced the title key synthetic intermediate. © 1990.