Reacción #220140

Ecuación de reacción

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

triphenylphosphine

DEAD

( 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

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

2-hydroxypyridine

→

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-(pyridin-2-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITAfter 2 min
2. 2
   workup.ADDITIONbuffer was added
3. 3
   Extracciónthe mixture was extracted with ethyl acetate
4. 4
   LavadoThe combined organic phases were washed with sat. aqueous NaCl
5. 5
   Secadodried (MgSO4)
6. 6
   Concentraciónconcentrated in vacuo

Procedimiento

Step 12 (A): (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-one. To a solution of triphenylphosphine (54 mg, 0.206 mmol) in THF (2.5 mL) at rt was added DEAD (0.0324 mL, 0.206 mmol). After 1 min, a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation K, 80 mg, 0.172 mmol) in THF (2.5 mL) was added. After 2 min, 2-hydroxypyridine (16.4 mg, 0.172 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 39.7 mg of the title compound as an opaque oil: 1H NMR (CDCl3, 300 MHz) δ 2.17-2.22 (1H, m), 2.32-2.42 (2H, m), 2.74 (1H, dd, J=3, 12 Hz), 3.20 (2H, m), 3.50 (1H, m), 3.78 (1H, m), 4.80 (1H, m), 4.97 (1H, s), 5.02 (1H, s), 5.38 (1H, m), 6.51 (2H, m), 6.66 (1H, m), 6.72 (1H, d, J=9 Hz), 6.81 (1H, t, J=6 Hz), 7.18-7.36 (10H, m), 7.52 (1H, m), 8.04 (1H, m). HPLC retention time: 1.52 min (method A). MS (ESI) (M+H)+ 542.15.

Fuente