Ethyl isobutyrate → 1-phenylmethyl-alpha,alpha-dimethyl-4-hydroxy-4-piperidine-acetic Acid Ethyl Ester

Temperature

-65 °C

To a solution of diisopropylamine (7.64 mL, 54.5 mmol) in dry tetrahydrofuran (5 mL) at −78° C. was added n-butyl lithium (2.5 M, 20 mL, 50.0 mmol). The mixture was stirred at −65° C. for 30 minutes. Then ethyl isobutyrate (6.09 mL, 45.6 mmol) in tetrahydrofuran (5 mL) was added. The mixture was stirred at −60° C. for 45 minutes. To this solution was added 1-benzylpiperidone (6.15 g, 32.5 mmol) in 5 mL of tetrahydrofuran. The mixture was allowed to warm up to room temperature and stirred overnight. The mixture was quenched with ammonium chloride solution (30 mL) and extracted with ether (100 mL). The organic layer was first washed with brine and then dried over sodium sulfate. Solvents were evaporated and the residue was purified using flash chromatography (eluting with ethyl acetate and hexanes) to give 2-(1-benzyl-4-hydroxy-piperidin-4-yl)-2-methyl-propionic acid ethyl ester (5.87 g) as an oily material. The NMR spectrum obtained on the sample is compatible with its structure. LC-MS calcd for C18H27NO3 (m/e) 305.43, obsd 306.2 (M+H).

1. stirringThe mixture was stirred at −60° C. for 45 minutes
2. temperatureto warm up to room temperature
3. stirringstirred overnight
4. customThe mixture was quenched with ammonium chloride solution (30 mL)
5. extractionextracted with ether (100 mL)
6. washThe organic layer was first washed with brine
7. dry with materialdried over sodium sulfate
8. customSolvents were evaporated
9. customthe residue was purified
10. washflash chromatography (eluting with ethyl acetate and hexanes)

ORD record

ord-4958e3db19544b6aaa8b120e26ab8c69

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153644B2