Benzene, ((2-bromoethoxy)methyl)- → Umeclidinium bromide

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (3.30 g, 11.2 mmol) in 2 CH3CN/3 CHCl3 (200 mL) was added 2-bromoethyl phenylmethyl ether (2.31 mL, 14.6 mmol). The solution was stirred at 60° C. for 16 h. The reaction was cooled down to room temperature and concentrated. EtOAc (200 mL) was added to the solid, and the mixture was allowed to stir for 1 hour then filtered. The resulting solid was taken up in MeOH (125 mL) and heated to 60° C. The solution was filtered hot, and then cooled back to room temperature. The reaction was concentrated to a low volume of MeOH (˜20 mL) and filtered. Water (75 mL) was then added and the resulting mixture was heated at 55° C. with brisk stirring for 40 min. After cooling to room temperature, the solid was filtered off, washed with water (20 mL) and dried in a vacuum oven at 45° C. for 16 hours to give the title compound (2.47 g, 43.3%). EI-MS m/z 428(M+) Rt (1.90 min) 1H NMR (DMSO-d6) δ 7.56 (d, 4H, J=1.2), 7.28 (m, 11H), 5.95 (s, 1H), 4.50 (s, 2H), 3.81 (d, 2H, J=4.0), 3.48 (t, 6H, J=7.2), 3.38 (d, 2H, J=4.0), 2.01 (t, 6H, J=7.2); Elemental analysis (C29H34NO2Br) C, H, N: calculated, 68.50, 6.74, 2.75. Found, 68.28, 6.68, 2.73.

Provenance & Evidence