Pyridine → Pyridinium chloride

Participants

Reaction Steps

In a manner similar to the method described in Example 3, 1-chloroethyl chloroformate (1.46 g, 1.1 mL, 10.2 mmol) was reacted with (2,2-dimethyl-[1,3]-dioxolan-4-yl)-methylamine (Aldrich, 1.21 g, 1.2 mL, 8.98 mmol) and pyridine (870 mg, 0.89 mL, 11.0 mmol) in methylene chloride (15 mL) at 78° C. for 3 h to give 1-chloroethyl (2,2-dimethyl-1,3-dioxolan-4-yl)methylcarbamate with pyridine hydrochloride (1:1). A portion of this material (622 mg, 1.76 mmol) in dimethylformamide (5 mL) was then reacted with chiral 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (201 mg, 0.326 mmol) in the presence of cesium carbonate (806.9 mg, 2.48 mmol) in dimethylformamide (7 mL) overnight to give 4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethylcarbamoyloxy)-ethyl ester as a white solid (97.7 mg, 36% yield). MS (ES+) m/z calcd. for C40H45C12F2N4O8: [(M+H)+]: 817, found: 817

Provenance & Evidence