Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate → (+/-)-tert-butyl 4-((1-(5-chloro-3-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Fluoroboric acid diethylether complex (0.015 g, 0.095 mmol) was added to a 0° C. solution of (±)-1-(5-chloro-3-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethyl 2,2,2-trichloroacetimidate (0.945 g, 1.907 mmol) and tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (0.59 g, 1.907 mmol) in Dichloromethane (10 mL) and was stirred for 20 min at 0° C. TLC indicated the reaction was complete, and the reaction was quenched with aqueous sodium bicarbonate (10 mL). The reaction was extracted with ethyl acetate (3×10 mL) and the organic phase was dried with MgSO4 and evaporated. The residue was purified by chromatography on SiO2 with 15%-20% ethyl acetate/hexanes to give (±)-tert-butyl 4-((1-(5-chloro-3-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (466 mg, 0.726 mmol, 38.0% yield) as a white solid. 1H-NMR (CDCl3, 400 MHz) δ 7.60 (d, J=2.0 Hz, 1H), 7.49 (s, 1H), 7.15 (m, 2H), 7.05 (d, J=2.0 Hz, 1H), 6.94 (app t, J=8.6 Hz, 2H), 5.22 (m, 2H), 5.07 (m, 1H), 3.66 (m, 2H), 3.33 (app t, J=8.3 Hz, 2H), 3.22 (d, J=8.8 Hz, 1H), 3.11 (d, J=8.8 Hz, 1H), 3.02 (m, 2H), 2.07 (m, 2H), 1.79 (m, 2H), 1.42 (d, J=6.3 Hz, 3H), 0.65-0.90 (m, 2H), −0.08 (s, 9H).

Provenance & Evidence