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

Participants

Reaction Steps

Step 15 (A): (3S,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,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation K, 60 mg, 0.129 mmol) in EtOH (5 mL) was added a solution of LiOH (62 mg, 2.58 mmol) in H2O (1.25 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 (8 mL) 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 to give the title compound (47.3 mg, 84% yield) as an opaque oil: 1H NMR (CDCl3, 300 MHz) δ 2.32-2.39 (1H, m), 2.49-2.62 (3H, m), 2.79-2.80 (1H, m), 3.18 (1H, d, J=12 Hz), 3.49-3.58 (2H, m), 4.28 (1H, t, J=6 Hz), 4.63 (1H, s), 5.55 (1H, s), 5.96 (4H, brd s), 6.62-6.68 (3H, m), 7.20-7.36 (6H, m), 7.77 (4H, d, J=6 Hz). HPLC retention time: 1.20 min (method A). MS (ESI) (M+H)+ 439.16.

Provenance & Evidence