3,5-Dimethyl-4-hydroxybenzaldehyde → 1-[(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-2-hydroxybutyl]-4-[(S)-3,5-dimethyl-4-(N-tert-butoxycarbonylpyrrolidine-2-carbonyloxy)benzyl]-1H-[1,2,4]triazol-4-ium bromide

Participants

Reaction Steps

A mixture of 1.06 g of (1R,2R)-4-[2-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]thiazol-4-yl]benzonitrile and 1.1 g of 3,5-dimethyl-4-[(S)-N-tert-butoxycarbonylpyrrolidine-2-carbonyloxy]benzyl bromide, prepared from 3,5-dimethyl-4-hydroxybenzaldehyde in 3 steps, in 20 mL of acetonitrile was stirred for 15 h at reflux temperature and then concentrated. The residue was chromatographed on silica gel (Wakogel C-200, solvent: CH2Cl2 /MeOH=12/1) to give 1.92 g (94%y.) of 1-[(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-2-hydroxybutyl]-4-[(S)-3,5-dimethyl-4-(N-tert-butoxycarbonylpyrrolidine-2-carbonyloxy)benzyl]-1H-[1,2,4]triazol-4-ium bromide as a white solid.

Provenance & Evidence