4-Amino-1-Boc-piperidine → tert-butyl 4-(5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-ylamino)piperidine-1-carboxylate

Participants

Reaction Steps

Tert-butyl 4-aminopiperidine-1-carboxylate (0.48 g, 2.4 mmol) and 5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-one (0.75 g, 2.0 mmol) were mixed in neat titanium(IV) isopropoxide (2.85 g, 10.0 mmol) and stirred at room temperature overnight. Methanol (10 mL) was added followed by addition of sodium borohydride (0.12 g, 3.2 mmol). The reaction was stirred at room temperature for 3 h and then quenched by adding 0.1N aqueous sodium hydroxide. The resulting mixture was filtered through celite, and the residue was washed with ethyl acetate (2×10 mL) and with dichloromethane (10 mL). The organic layer was separated and dried over sodium sulfate. The drying agent was filtered off, and the filtrate concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, ethyl acetate/hexanes=1/4) to afford the title compound as a off-white solid (0.73 g, 65%). 1H NMR (CDCl3, 300 MHz) 7.64 (m, 1H), 7.48 (m, 2H), 6.95 (m, 2H), 6.76 (m, 2H), 4.68 (m, 1H), 4.44 (m, 1H), 3.53 (m, 2H), 3.18 (m, 2H), 2.85 (m, 4H), 2.47 (m, 2H), 2.24-1.79 (m, 12H), 1.46 (s, 9H) ppm; MS (ES) 560.6 (M+H).

Provenance & Evidence