4-Acetyl-4-(4-chloro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester → 4-(4-Chloro-phenyl)-4-(1-hydroxy-1-methyl-ethyl)-piperidine-1-carboxylic acid tert-butyl ester

Temperature

0 °C

To a dry round bottom flask was added via syringe 16 ml methyl magnesium bromide in toluene/tetrahydrofuran (75:25, 1.4 M). The flask was cooled in an ice bath under a stream of nitrogen. A solution 4-acetyl-4-(4-chloro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (337 mg, 1.02 mmol) in 5 ml tetrahydrofuran was added dropwise to the flask over 20 minutes and the resulting mixture was stirred at 0° C. for 8 hours. The reaction mixture was warmed to room temperature and stirred for 5 days. The reaction was quenched by slow addition of 150 ml saturated aqueous ammonium chloride and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate and concentrated under vacuum. The yellow residue was purified by silica gel chromatography, eluting with hexane-ethyl acetate (7.5:2.5) to give the title compound (242 mg, 67%).

1. temperatureThe flask was cooled in an ice bath under a stream of nitrogen
2. temperatureThe reaction mixture was warmed to room temperature
3. stirringstirred for 5 days
4. customThe reaction was quenched by slow addition of 150 ml saturated aqueous ammonium chloride
5. extractionextracted with ethyl acetate
6. washThe combined organic phases were washed with brine
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated under vacuum
9. customThe yellow residue was purified by silica gel chromatography
10. washeluting with hexane-ethyl acetate (7.5:2.5)

ORD record

ord-22abbbf30fff46f0b22cd1fb687a9a03

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07186729B2