Reaction #49217

Reaction equation

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

LiOH

( 8 )

(4S,5R)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)pyrrolidin-2-yl)oxazolidin-2-one

(1S,2S)-2-Amino-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)propan-1-ol

→

title compound

Yield 95.7%

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

Yield 95.7%

Solvents

EtOH

H2O

Conditions

Workup

1. 1
   Otherwas brought to 98° C.
2. 2
   OtherSolvent was removed
3. 3
   workup.ADDITION1N HCl solution (50 mL) was added to the mixture
4. 4
   Washwashed with diethyl ether
5. 5
   ExtractionThis mixture was extracted with ethyl acetate
6. 6
   DryingThe combined organic layer was dried (Na2SO4)
7. 7
   Concentrationconcentrated in vacuo

Procedure

Step D (8): (1S,2S)-2-Amino-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)propan-1-ol. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((R)-4-benzhydrylmorpholin-3-yl)oxazolidin-2-one (step D (7), 85 mg, 0.18 mmol) in EtOH (2 mL) was added a solution of LiOH (66 mg, 2.75 mmol) in H2O (1 mL). This reaction mixture was brought to 98° C. and stirred for overnight. Solvent was removed and 1N HCl solution (50 mL) was added to the mixture and washed with diethyl ether. The aqueous phase was basified with 50% aqueous NaOH solution. This mixture was extracted with ethyl acetate. The combined organic layer was dried (Na2SO4), and concentrated in vacuo to give 80 mg of the title compound: 1H NMR (CDCl3, 500 MHz) δ 1.94-2.06 (3H, m), 2.30 (1H, dd, J=10, 15 Hz), 2.51-2.59 (1H, m), 2.73-2.81 (1H, m), 2.90 (1H, m), 2.95 (1H, m), 3.08 (1H, m), 3.70 (1H, m), 3.80 (1H, dt, J=5, 10 Hz), 3.91 (1H, m), 4.09 (1H, m), 4.14 (1H, m), 5.05 (1H, s), 6.60-6.68 (3H, m), 7.15-7.31 (6H, m), 7.37 (2H, d, J=10 Hz), 7.42 (2H, d, J=5 Hz). MS (ESI) (M+H)+ 439.20.

Source