反应详情

To a mixture of rac-4-({[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-cyclohexanecarboxylic acid methyl ester (65.0 mg, 0.105 mmol, example 21) in THF (4 mL) was added a solution of LiOH (Aldrich, 31.5 mg, 0.75 mmol) in water (2 mL) and the reaction mixture was stirred at rt for 6.5 hrs then more THF (2 mL) and water (1 mL) was added and stirred for 6 more hrs. The reaction mixture was partly concentrated and quenched with 1 N HCl (pH 5-6), extracted with EtOAc, and washed with water, saturated NaCl. The organic phase was separated, and dried over Na2SO4. The mixture was then concentrated to rac-4-({[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]amino}-methyl)-cyclohexanecarboxylic acid (95.8 mg, 100%). HRMS (ES+) m/z Calcd for C31H35Cl2F2N3O3+H [(M+H)+]: 606.2097; Found: 606.2097.

1. stirringstirred for 6 more hrs
2. concentrationThe reaction mixture was partly concentrated
3. customquenched with 1 N HCl (pH 5-6)
4. extractionextracted with EtOAc
5. washwashed with water, saturated NaCl
6. customThe organic phase was separated
7. dry with materialdried over Na2SO4
8. concentrationThe mixture was then concentrated to rac-4-({[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]amino}-methyl)-cyclohexanecarboxylic acid (95.8 mg, 100%)