1,1'-Carbonyldiimidazole → (R)-3-[3,5-Dichloro-4'-(4,4-difluoro-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one

Participants

Reaction Steps

Treat a solution of (R)-3′,5′-dichloro-4′-[2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic acid (4.0 g, 6.45 mmol) in CH2Cl2 (40 mL) with 1,1′-carbonyldiimidazole (2.09 g, 12.91 mmol) and stir for 1 hour at room temperature. Treat the reaction with 4,4-difluoropiperidine hydrochloride (1.53 g, 9.68 mmol) and diisopropylethylamine (1.69 g, 9.68 mmol) and stir for 12 hours at room temperature. Load the mixture on silica gel column and flash with 25% to 35% ethyl acetate in hexanes to afford 3.8 g (81%) of the title compound. MS (m/z): 722 (M+).

Provenance & Evidence