反应详情

A mixture of rac-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetic acid (0.2 g, 0.41 mmol), 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.15 g, 1 mmol), HATU (0.23 g, 0.6 mmol) and iPr2NEt (0.29 mL, 1.68 mmol) in CH2Cl2 (30 mL) was stirred at room temperature for 20 h. The reaction mixture was quenched with water was and the organic layer was separated, the aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over Na2SO4, and concentrated. The residue was dissolved into tetrahydrofuran (7 mL), and aqueous HCl solution (1 N, 3 mL, 3 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 0.5 h. The solvent was removed, and the residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution. The organic layer was separated, washed with water, brine, dried over Na2SO4, and concentrated. The residue was purified by chromatography (5% MeOH in EtOAc) to give rac-2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-N—((S)-3,4-dihydroxy-butyl)-acetamide as an off-white solid (0.1 g, 42%). HRMS (ES+) m/z Calcd for C28H33Cl2F2N3O3+H [(M+H)+]: 568.1940; Found: 568.1943.

1. customThe reaction mixture was quenched with water
2. customthe organic layer was separated
3. extractionthe aqueous layer was extracted with ethyl acetate
4. dry with materialdried over Na2SO4
5. concentrationconcentrated
6. additionwas added to the solution
7. stirringThe reaction mixture was stirred at room temperature for 0.5 h
8. customThe solvent was removed
9. customthe residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution
10. customThe organic layer was separated
11. washwashed with water, brine
12. dry with materialdried over Na2SO4
13. concentrationconcentrated
14. customThe residue was purified by chromatography (5% MeOH in EtOAc)