Reacción #220141

Ecuación de reacción

(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-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

( B )

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

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

→

title compound

Rendimiento 93.0%

(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-(pyridin-2-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

Rendimiento 93.0%

Disolventes

EtOH

H2O

MeOH chloroform

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaat reflux for 4 h
2. 2
   Concentraciónthe mixture was concentrated
3. 3
   Otroto remove EtOH and H2O
4. 4
   workup.ADDITIONwas added
5. 5
   ExtracciónThe mixture was extracted with ethyl acetate
6. 6
   Lavadothe organic phase was washed with sat. aqueous NaCl
7. 7
   Secadodried (MgSO4)
8. 8
   Concentraciónconcentrated in vacuo

Procedimiento

Step 12 (B): (1S,2S)-2-amino-1-((2R,4R)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-one (Step 12 (A), 39.2 mg, 0.072 mmol) in EtOH (3 mL) was added a solution of LiOH (35 mg, 1.44 mmol) in H2O (0.75 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 34.5 mg (93% yield) of the title compound as a clear oil: 1H NMR (CDCl3, 300 MHz) δ 2.12-2.31 (3H, m), 2.44 (1H, m), 2.64 (1H, dd, J=6, 12 Hz), 2.80 (1H, m), 2.99-3.09 (2H, m), 3.30-3.38 (2H, m), 4.98 (1H, s), 5.36 (1H, m), 6.60-6.73 (3H, m), 6.79-6.86 (2H, m), 7.11-7.39 (9H, m), 7.45-7.47 (1H, m), 7.58 (1H, m), 8.06 (1H, m). HPLC retention time: 1.55 min (method A). MS (ESI) (M+H)+ 516.24.

Fuente