反应详情

Tert-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate (300 mg, 0.65 mmol) dissolved in DCM (15 ml) and added Trifluoroacetic acid (1.5 ml). This mixture was stirred at rt for 2 h. DCM removed from the reaction mixture to obtain 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (300 mg). 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (150 mg, 0.31 mmol) was dissolved in DMF (2.6 ml) and added N,N-Carbonyl diimidazole (101 mg, 0.63 mmol) and stirred at rt for 1 h. To this mixture added cyclobutanol (0.05 ml, 0.63 mmol) and TEA (0.13 ml, 0.94 mmol) and stirred at 60° C. for overnight. Work up (EtOAc/H2O) and purification of the crude by combiflash with gradient mixture of ethyl acetate and petether (1:1) as eluent afforded the titled compound (25 mg) as an off-white solid. M.P.: 165-169° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.04 (s, 1H), 7.88 (s, 1H), 7.72-7.58 (m, 4H), 7.55-7.50 (m, 1H), 4.96 (septet, J 7.8, 1H), 4.20 (d, J 12.4, 2H), 3.22-3.13 (m, 1H), 3.06 (t, J 9.8, 2H), 2.40-2.30 (m, 2H), 2.24-2.15 (m, 2H), 2.15-2.02 (m, 2H), 2.00-1.90 (m, 2H), 1.78 (q, J 10, 2H).

1. customDCM removed from the reaction mixture