Reaction #43616

Reaction equation

racemic ethyl 4-hydroxy-1-(phenylmethyl)-3-piperidinecarboxylate

tert-butyldimethylchlorosilane

imidazole

water

→

desired compound

Yield 45.0%

ethyl(cis)-4-hydroxy-1-(phenylmethyl)-3-piperidinecarboxylate

Yield 45.0%

ethyl(trans)-4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-(phenylmethyl)-3-piperidinecarboxylate

Yield 30.0%

Solvents

ethyl acetate

hexane

N,N-dimethylformamide

Conditions

Workup

1. 1
   Extractionthe aqueous phase was extracted with dichloromethane
2. 2
   OtherThe organic layer was dried
3. 3
   Otherthe solvent was removed under reduced pressure
4. 4
   Otherto afford 40 g of crude

Procedure

To a solution of racemic ethyl 4-hydroxy-1-(phenylmethyl)-3-piperidinecarboxylate (37 g, 140 mmol) in N,N-dimethylformamide (250 ml) was added tert-butyldimethylchlorosilane (10.6 g, 70 mmol) and imidazole (5.3 g, 77 mmol) under argon. The reaction was stirred at room temperature for 3 h; water was added and the aqueous phase was extracted with dichloromethane. The organic layer was dried and the solvent was removed under reduced pressure to afford 40 g of crude. The crude was divided into 3 batches (5 g, 17 g, 17 g) and each batch was subjected to column chromatography on silica gel using a hexane and ethyl acetate gradient (0-20% ethyl acetate in hexane). This provided the desired compound (16.67 g, 45%) and ethyl(trans)-4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-(phenylmethyl)-3-piperidinecarboxylate (15.8 g, 30%).

Source