Triphenylphosphine → (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 (A): (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-one. To a solution of triphenylphosphine (58 mg, 0.22 mmol) in THF (2.5 mL) at rt was added DEAD (0.035 mL, 0.22 mmol). After 1 min, a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation J, 85 mg, 0.183 mmol) in THF (2.5 mL) was added. After 2 min, 2-hydroxypyridine (17.4 mg, 0.183 mmol) was added and the mixture was stirred at rt for 3.5 h. pH 7 buffer was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Flash chromatography (silica gel, 0-100% ethyl acetate/hexane) gave 50.7 mg (52% yield) of the title compound: 1H NMR (CDCl3, 300 MHz) δ 2.22 (1H, m), 2.38-2.55 (3H, m), 2.87 (1H, d, J=12 Hz), 3.32 (1H, dd, J=6, 12 Hz), 3.56-3.63 (2H, m), 4.70 (1H, d, J=9 Hz), 4.96 (1H, s), 5.42 (1H, s), 5.51 (1H, s), 6.47-6.53 (2H, m), 6.62-6.73 (3H, m), 6.81 (1H, t, J=6 Hz), 7.13-7.28 (5H, m), 7.37-7.42 (4H, m), 7.54 (1H, m), 8.08 (1H, m). HPLC retention time: 1.73 min (method C). MS (ESI) (M+H)+ 542.31.

Provenance & Evidence