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-phenoxypyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

Step 9 (B): (1S,2S)-2-amino-1-((2R,4S)-1-benzhydryl-4-phenoxypyrrolidin-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-phenoxypyrrolidin-2-yl)oxazolidin-2-one (Step 9 (A), 57 mg, 0.11 mmol) in EtOH (5 mL) was added a solution of LiOH (53 mg, 2.2 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 41.1 mg (73% yield) of the title compound: 1H NMR (CDCl3, 300 MHz) δ 2.05-2.12 (1H, m), 2.21-2.30 (1H, m), 2.39 (1H, m), 2.62-2.72 (2H, m), 2.90-2.99 (2H, m), 3.39 (1H, dd, J=3, 12 Hz), 3.69 (1H, m), 4.80 (1H, m), 5.07 (1H, s), 6.65-6.68 (3H, m), 6.82 (2H, m), 6.93 (1H, m), 7.14 (1H, m), 7.20-7.31 (7H, m), 7.35-7.38 (4H, m). HPLC retention time: 1.65 min (method C). MS (ESI) (M+H)+ 515.35.

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

ORD 기록

ord-d77bfa96eb004beaac54efffcf592249

출처 데이터셋

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07388007B2