Réaction #220133

Équation de réaction

(1S,2S)-2-amino-1-((2R,4S)-1-benzhydryl-4-phenoxypyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-phenoxypyrrolidin-2-yl)oxazolidin-2-one

(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamide

LiOH

MeOH chloroform

→

title compound

Rendement 73.0%

(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

Rendement 73.0%

Solvants

EtOH

H2O

Conditions de réaction

Traitement

1. 1
   Températureat reflux for 4 h
2. 2
   Concentrationthe mixture was concentrated
3. 3
   Autreto remove EtOH and H2O
4. 4
   workup.ADDITIONwas added
5. 5
   ExtractionThe mixture was extracted with ethyl acetate
6. 6
   Lavagethe organic phase was washed with sat. aqueous NaCl
7. 7
   Séchagedried (MgSO4)
8. 8
   Concentrationconcentrated in vacuo

Mode opératoire

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.

Source