Hydrochloric Acid → 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-(trifluoromethyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

In a 50 mL round-bottomed flask, methyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-(trifluoromethyl)benzoate (290 mg, 434 μmol, Eq: 1.00) was combined with THF (8 ml) and MeOH (8.00 ml) to give a colorless solution. 1.5 M NaOH (3 ml, 4.5 mmol, Eq: 10.4) was added. The reaction mixture was heated to 50° C. and stirred for 3 h. The reaction mixture was acidified with 1N HCl and was extracted with EtOAc (3×15 mL). The organic layers were combined, washed with saturated NaCl (1×10 mL), dried over Na2SO4 and concentrated in vacuum. The crude material was dissolved in DMSO and purified by preparative HPLC (70-100% ACETONITRILE/water). Obtained was a white solid (130 mg, 46% yield). MS (ES+) m/z Calcd: [(M+H)+]: 654. found: 654.

Provenance & Evidence