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

Participants

Reaction Conditions

Reaction Steps

A solution of 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (31.7 kg) and benzyl 2-bromoethyl ether (25.7 kg) in n-propanol (257.5 kg) was refluxed for 13 hours. The solution was cooled to 50-55° C. over not less than an hour and stirred for 40 minutes to induce crystallisation. The slurry was cooled to 17-23° C. over not less than 1 hour and stirred for 60 minutes. The slurry was then cooled to 0-5° C. over not less than 1 hour and aged for 2 hours. The product was filtered and washed twice with n-propanol (34.8 kg and 33.8 kg). Drying under vacuum at 50° C. gave a white solid (47.95 kg, 87%).

Provenance & Evidence