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,4R)-4-hydroxypyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

Participants

Reaction Steps

Step 14 (A): (3R,5R)-5-((1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)-1-benzhydrylpyrrolidin-3-ol. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation J, 129 mg, 0.278 mmol) in EtOH (10 mL) was added a solution of LiOH (133 mg, 5.56 mmol) in H2O (2.5 mL). This reaction mixture was stirred at reflux for 3.5 h. After cooling down to rt, the mixture was concentrated to remove EtOH and 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 the title compound: 1H NMR (CDCl3, 500 MHz) δ 2.00-2.05 (1H, m), 2.13-2.21 (1H, m), 2.40-2.61 (2H, m), 2.79-2.91 (2H, m), 3.21 (2H, d, J=15 Hz), 3.51 (1H, d, J=15 Hz), 4.26 (1H, m), 4.79 (1H, s), 6.62-6.70 (3H, m), 7.14-7.26 (4H, m), 7.30-7.35 (3H, m), 7.37-7.43 (3H, m). HPLC retention time: 1.19 min (method A). MS (ESI) (M+H)+ 439.22.

Provenance & Evidence