反应详情

Step 12 (B): (1S,2S)-2-amino-1-((2R,4R)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-one (Step 12 (A), 39.2 mg, 0.072 mmol) in EtOH (3 mL) was added a solution of LiOH (35 mg, 1.44 mmol) in H2O (0.75 mL). This reaction mixture was stirred at reflux for 4 h. After cooling down to rt, the mixture was concentrated to remove EtOH and H2O was added followed by 1N HCl solution and pH 7 buffer. The mixture was extracted with ethyl acetate and the organic phase was washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Flash chromatography (silica gel, 0-10% MeOH/chloroform) gave 34.5 mg (93% yield) of the title compound as a clear oil: 1H NMR (CDCl3, 300 MHz) δ 2.12-2.31 (3H, m), 2.44 (1H, m), 2.64 (1H, dd, J=6, 12 Hz), 2.80 (1H, m), 2.99-3.09 (2H, m), 3.30-3.38 (2H, m), 4.98 (1H, s), 5.36 (1H, m), 6.60-6.73 (3H, m), 6.79-6.86 (2H, m), 7.11-7.39 (9H, m), 7.45-7.47 (1H, m), 7.58 (1H, m), 8.06 (1H, m). HPLC retention time: 1.55 min (method A). MS (ESI) (M+H)+ 516.24.

1. temperatureat reflux for 4 h
2. concentrationthe mixture was concentrated
3. customto remove EtOH and H2O
4. additionwas added
5. extractionThe mixture was extracted with ethyl acetate
6. washthe organic phase was washed with sat. aqueous NaCl
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo