Bromoacetonitrile → (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (3.5 g, 10.2 mmol) in CH3CN (140 mL), NaH (1.2 g, 30.6 mmol) was added at 0° C. The mixture was stirred for 1 hr. Then the mixture was cooled to −20° C., bromoacetonitrile (3.6 g, 30.6 mmol) was added dropwise. The mixture was allowed warm to 0° C. gradually. Another batch of NaH and bromoacetonitrile was added in the same manner. The mixture was quenched with H2O and extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrate to give the crude (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate (4.4, 100%).

Provenance & Evidence