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

Participants

Reaction Steps

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.

Provenance & Evidence