Benzylamine → Carvedilol

Participants

Reaction Steps

To 400 ml ethylacetate, 70 g (0.27 moles) anhydrous N-2-[2-(methoxy)-phenoxy]-ethyl]-benzylamine, 10.25 g (0.075 moles) of anhydrous ZnCl2 and 50 g (0.21 moles) of 4-(oxiranylmethoxy)-9H-carbazole are added and the reaction mixture is heated to 70-75° C. for 3 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture is cooled to ambient temperature and quenched into 100 ml of ˜12-15% aqueous ammonia. The aqueous layer separated, and the product enriched organic layer is washed with water till neutral pH. The organic layer is charcoalised, filtered and the filtrate subjected to hydrogenation reaction. To this solution of N-benzyl carvedilol in ethylacetate, 5 ml acetic acid is added, followed by (7 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 4.0 Kg/cm2 at temperature of 60-70° C. for a period of about 8 hours. The reaction mixture is filtered and the filtrate is washed with 40 ml of 12-15% v/v aqueous ammonia. The product enriched organic layer is separated and concentrated to remove ethylacetate. To the resultant syrupy mass n-butanol (100 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (50 ml) and toluene (100 ml) to obtain carvedilol (55.4 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (49 g).

Provenance & Evidence