反应详情

To a solution of rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl chloride (0.34 g, 0.7 mmol) in tetrahydrofuran (5 mL) was added 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.1 g, 0.71 mmol) and triethylamine (0.15 mL, 1 mmol). The reaction mixture was stirred at room temperature for 30 min. An aqueous HCl solution (1 N, 5 mL, 5 mmol) was added. The reaction mixture was stirred at room temperature for 1 h. The solvents were removed and the residue was partitioned between ethyl acetate and NaHCO3 (sat.) solution. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by column chromatography (EtOAc) to afford rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide as a white solid (0.11 g, 28%). HRMS (ES+) m/z Calcd for C27H31Cl2F2N3O3+H [(M+H)+]: 554.1784; Found: 554.1785.

1. stirringThe reaction mixture was stirred at room temperature for 1 h
2. customThe solvents were removed
3. customthe residue was partitioned between ethyl acetate and NaHCO3 (sat.) solution
4. customThe organic layer was separated
5. washwashed with water, brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. customThe residue was purified by column chromatography (EtOAc)