Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate → HCID 57546117, compound

Participants

Reaction Conditions

Reaction Steps

(±)-1-(3-Bromo-5-(trifluoromethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethyl 2,2,2-trichloroacetimidate (1.29 g, 2.21 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (0.71 g, 2.43 mmol) were combined in a dichloromethane/cyclohexane mixture (1:1, 8 mL) and cooled to 0° C. The reaction was treated with tetrafluoroboric acid-diethyl ether complex (60 μL, 0.44 mmol), stirred at 0° C. for 1 h, quenched by addition of saturated sodium bicarbonate and diluted with diethyl ether and the layers separated. The ethereal was washed with water (2×), 1 M potassium bisulfate (2×), brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (10% ethyl acetate/hexanes) gave 840 mg (53%) as a yellow film. 1H-NMR (CDCl3, 500 MHz) δ 7.82 (s, 1H), 7.54 (s, 1H), 7.24-7.27 (m, 2H), 7.18-7.22 (m, 3H), 5.51 (s, 2H), 5.07 (q, J=6.4 Hz, 1H), 3.74 (m, 2H), 3.44-3.51 (m, 2H), 3.27 (d, J=9.2 Hz, 1H), 3.24 (d, J=9.2 Hz, 1H), 2.99-3.03 (m, 2H), 2.11-2.16 (m, 2H), 1.82-1.88 (m, 2H), 1.50 (d, J=6.4 Hz, 3H), 1.43 (s, 9H), 0.70-0.83 (m, 2H), 0.08 (s, 9H). Mass spec.: 736.03 (MNa)+.

Provenance & Evidence