反应详情

A mixture of rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methylsulfanyl-propyl)-amide (119.2 mg, 0.23 mmol) and dichloromethane (2 mL) was added to a solution of refluxing acetic acid (5 mL, 79.4 mmol) and 30% hydrogen peroxide (2 mL) for 5 min. The reaction mixture was cooled to room temperature and stored in the freezer overnight. The mixture was diluted with water and dichloromethane, the organic layer was separated and solvent removed under reduced pressure. The resulting oil was carried directly to the next step by adding acetic acid (5 mL, 79.4 mmol) and zinc dust (0.85 g, 13 mmol). After stirring at room temperature for 3 h, an additional amount of zinc dust (0.85 g, 13 mmol) was added and stirred for an additional 3 h at room temperature. Reaction worked up by filtration through celite, washing with dichloromethane (50 mL). The filtrate was washed with water (2×) and the organic layer was separated, dried with MgSO4, filtered and the solvent evaporated under reduced pressure to yield crude oil. Purification by reverse phase chromatography (20-95% of ACN/water) to give rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methanesulfonyl-propyl)-amide (36.5 mg, 28.8%) as an off-white powder. HRMS (ES+) m/z Calcd for C27H33Cl2N3O3S+H [(M+H)+]: 550.1693. found: 550.1692.

1. customstored in the freezer overnight
2. customthe organic layer was separated
3. customsolvent removed under reduced pressure
4. stirringstirred for an additional 3 h at room temperature
5. customReaction
6. filtrationworked up by filtration through celite
7. washwashing with dichloromethane (50 mL)
8. washThe filtrate was washed with water (2×)
9. customthe organic layer was separated
10. dry with materialdried with MgSO4
11. filtrationfiltered
12. customthe solvent evaporated under reduced pressure
13. customto yield crude oil
14. customPurification by reverse phase chromatography (20-95% of ACN/water)