Reaction #49216

Reaction equation

(4S,5S)-4-(3,5-difluorobenzyl)-5-(morpholin-3-yl)oxazolidin-2-one

(2S,3 S)-2-(3,5-difluorobenzyl)-3-((2R,4R)-4-(allyloxy)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-3-hydroxypropanoic acid

potassium carbonate

bromodiphenylmethane

( 7 )

(2R,4R)-tert-butyl 2-((4S,5 S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)-4-(allyloxy)pyrrolidine-1-carboxylate

(4S,5S)-4-(3,5-Difluorobenzyl)-5-((R)-4-benzhydrylmorpholin-3-yl)oxazolidin-2-one

→

title compound

Yield 29.0%

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

Yield 29.0%

Solvents

acetonitrile

Conditions

Workup

1. 1
   OtherSolvent was removed
2. 2
   Otherthe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 65% EtOAc/Hexane step gradient)

Procedure

Step D (7): (4S,5S)-4-(3,5-Difluorobenzyl)-5-((R)-4-benzhydrylmorpholin-3-yl)oxazolidin-2-one. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-(morpholin-3-yl)oxazolidin-2-one (step D (6), 180 mg, 0.6 mmol) in acetonitrile (5 mL) were added potassium carbonate (248 mg, 1.8 mmol) and bromodiphenylmethane (296 mg, 1.2 mmol). This mixture was stirred at 100° C. for 1.5 h. Solvent was removed and the crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 65% EtOAc/Hexane step gradient) to give 85 mg of the title compound (29% yield): 1H NMR (CDCl3, 500 MHz) δ 2.14 (1H, m), 2.76 (2H, d, J=15 Hz), 2.98 (1H, d, J=5 Hz), 3.15 (1H, m), 3.52 (1H, m), 3.67 (1H, m), 3.87-3.94 (3H, m), 5.23 (2H, d, J=10 Hz), 5.31 (1H, m), 6.56 (2H, d, J=5 Hz), 6.70 (1H, m), 7.16 (1H, d, J=5 Hz), 7.21-7.37 (7H, m), 7.41 (2H, d, J=10 Hz). MS (ESI) (M+H)+ 465.14.

Source