tert-Butyl 4-formylpiperidine-1-carboxylate → tert-butyl 4-((2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(hydroxy)methyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amine (115 mg, 0.21 mmol) in THF (0.5 mL) at 0° C. was added i-PrMgCl/LiCl (0.3 mL, 0.39 mmol). The mixture was stirred 0° C. for 3 hours and tert-butyl 4-formylpiperidine-1-carboxylate (70.7 mg, 0.33 mmol) in THF (0.1 mL) was added. The mixture was stirred at 0° C. to room temperature for 3 hours and quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate. Combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by chromatography over 25+S Biotage silica column (eluted with 0-50% ethyl acetate in hexanes) to afford the title compound (62.2 mg, 44%). 1H NMR (400 MHz, CDCl3) δ ppm 1.12-1.19 (m, 1H) 1.20-1.32 (m, 1H) 1.43 (s, 9H) 1.69-1.78 (m, 1H) 1.89 (dd, J=13.07, 1.87 Hz, 1H) 2.46-2.67 (m, 2H) 3.99-4.15 (m, 2H) 4.18 (s, 3H) 4.66-4.73 (m, 2H) 4.68-4.83 (m, 4H) 4.87 (d, J=15.77 Hz, 1H) 7.33 (s, 1H) 7.55 (s, 2H) 7.64 (s, 2H) 7.77 (s, 1H). MS (ES+) Calc: 696.2, Found: 697.6 (M+1)

Provenance & Evidence