Reacción #220138

Ecuación de reacción

( 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-phenoxypyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

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

( A )

(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

→

title compound

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

Disolventes

EtOH

H2O

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 11 (B): (1S,2S)-2-amino-1-((2R,4R)-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,4R)-1-benzhydryl-4-phenoxypyrrolidin-2-yl)oxazolidin-2-one (Step 11 (A), (34.7 mg, 0.064 mmol) in EtOH (3 mL) was added a solution of LiOH (31 mg, 1.28 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 29 mg of the title compound: 1H NMR (CDCl3, 300 MHz) δ 2.16-2.29 (2H, m), 2.49-2.59 (2H, m), 2.78-3.42 (8H, m), 4.68 (1H, s), 4.95 (1H, s), 6.63-6.74 (3H, m), 6.88-6.93 (2H, m), 6.95-6.98 (1H, m), 7.09-7.36 (11H, m), 7.46-7.48 (1H, m). HPLC retention time: 1.59 min (method A). MS (ESI) (M+H)+ 515.19.

Fuente