Piperidine → 1-(4-Bromo-2,6-difluorobenzyl)-piperidine

Methane sulfonyl chloride (0.38 mL, 4.93 mmol) was added dropwise to a cooled (0° C.) solution of (4-bromo-2,6-difluorophenyl)-methanol (1.00 g, 4.48 mmol) and triethylamine (0.75 mL, 5.38 mmol) in DCM (50 mL). The reaction mixture was allowed to warm to ambient temperature and stirred for 2 h. The mixture was diluted with DCM (30 mL) and washed with water (20 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford a colourless oil. The oil was dissolved in acetonitrile (30 mL), piperidine (0.53 mL, 5.38 mmol) and potassium carbonate (0.93 g, 6.72 mmol) were added and the reaction mixture was heated at 50° C. for 90 minutes. The reaction mixture was allowed to cool to ambient temperature and the solid removed by filtration. The filtrate was evaporated in vacuo and the resultant residue purified by flash column chromatography (silica, 12 g column, ISCO, 0-40% ethyl acetate in cyclohexane) to afford the title compound as a colourless oil (1.23 g, 99%). 1H NMR (CDCl3, 300 MHz): 7.07 (d, J=6.6 Hz, 2H), 3.62 (t, J=1.7 Hz, 2H), 2.41 (t, J=5.1 Hz, 4H), 1.59-1.50 (m, 4H), 1.42-1.33 (m, 2H). LCMS (Method B): RT=1.67 min, M+H+=290/292.

1. washwashed with water (20 mL)
2. customThe organic phase was separated
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. customevaporated in vacuo
6. customto afford a colourless oil
7. temperaturethe reaction mixture was heated at 50° C. for 90 minutes
8. temperatureto cool to ambient temperature
9. customthe solid removed by filtration
10. customThe filtrate was evaporated in vacuo
11. customthe resultant residue purified by flash column chromatography (silica, 12 g column, ISCO, 0-40% ethyl acetate in cyclohexane)

ORD record

ord-0b6abb72bbdc4cada3d67208621bc6da

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501765B2