Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate → Tert-butyl 4-(((5-bromopryidin-3-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

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tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyllpiperidine-1-carboxylate. 2-(bromomethyl)-6-chloro-4-(trifluoromethyl)pyridine (301 mg, 1.1 mmol) and tert-butyl 4-(hydroxymethyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (309 mg, 1.0 mmol) were combined in tetrahydrofuran (20 mL) and cooled to 0° C. The reaction was treated with potassium tert-butoxide (244 mg, 2.0 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 215 mg (43%). 1H-NMR (CDCl3, 400 MHz) δ 7.38 (s, 1H), 7.29-7.36 (m, 2H), 7.14 (s, 1H), 7.01-7.10 (m, 2H), 4.48 (s, 2H), 3.74-3.79 (m, 2H), 3.47 (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.: 403.08 (MH)+.

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