Hexane → (R)-tert-butyl 3-(2-(benzyloxy)-3,5-difluorobenzoyl)piperidine-1-carboxylate

Temperature

-78 °C

To a solution of 2-(benzyloxy)-1-bromo-3,5-difluorobenzene (13.7 g, 46 mmol) in anhydrous THF (100 mL) at −78° C. under nitrogen was added dropwise a solution of 2.5 M n-BuLi in hexane (18.4 mL, 46 mmol). After stirring for 1 hr at −78° C., a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (10.43 g, 38.3 mmol) in anhydrous THF (40 mL) was added dropwise. After addition, the reaction mixture was allowed to warm to rt and stirred for 2 h. The mixture was quenched with saturated NH4Cl solution (100 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with AcOEt/hexane (1:20→1:10) to provide (R)-tert-butyl 3-(2-(benzyloxy)-3,5-difluorobenzoyl)piperidine-1-carboxylate (6.4 g, 32%) as a light yellow oil.

1. additionAfter addition
2. temperatureto warm to rt
3. stirringstirred for 2 h
4. customThe mixture was quenched with saturated NH4Cl solution (100 mL)
5. extractionextracted with ethyl acetate (3×50 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography on silica gel eluting with AcOEt/hexane (1:20→1:10)

ORD record

ord-93cb25297b8b4a82bb8da21a1d0fe918

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08487108B2