Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate → Tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

2-(bromomethyl)-6-chloro-4-(trifluoromethyl)pyridine (1.1 g, 4.1 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (1.0 g, 3.4 mmol) were combined in tetrahydrofuran (20 mL) and cooled to 0° C. The reaction was treated with potassium tert-butoxide (763 mg, 6.8 mmol) portion wise. The reaction was stirred at 0° C. for 1 hr. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over magnesium sulfate, and concentrated. Column chromatography on silica gel (10% ethyl acetate/hexanes) gave 837 mg (52%). 1H-NMR (CDCl3, 400 MHz) δ 7.31-7.38 (m, 6H), 7.18 (s, 1H), 4.48 (s, 2H), 3.74-3.79 (m, 2H), 3.50 (s, 2H), 2.99-3.06 (m, 2H), 2.21-2.25 (m, 2H), 1.83-1.86 (m, 2H), 1.42 (s, 9H). Mass spec.: 485.11 (MH)+.

Provenance & Evidence