Lithium Hydroxide → (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4S)-4-(pyridin-2-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

Participants

Reaction Steps

Step 10 (B): (1S,2S)-2-amino-1-((2R,4S)-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,4S)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-one (Step 10 (A), 50 mg, 0.092 mmol) in EtOH (5 mL) was added a solution of LiOH (44 mg, 1.84 mmol) in H2O (1.5 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 29.0 mg (61% yield) of the title compound: 1H NMR (CDCl3, 300 MHz) δ 2.03-2.11 (2H, m), 2.23-2.42 (2H, m), 2.69 (2H, s), 2.92-2.97 (2H, m), 3.48 (1H, dd, J=3, 12 Hz), 3.73 (1H, m), 5.07 (1H, s), 5.44 (1H, s), 6.61-6.68 (4H, m), 6.82 (1H, m), 7.12-7.29 (6H, m), 7.32-7.44 (4H, m), 7.54 (1H, m), 8.06 (1H, dd, J=3, 6 Hz). HPLC retention time: 1.54 min (method C). MS (ESI) (M+H)+ 516.35.

Provenance & Evidence