Benzylamine → Carvedilol

Participants

Reaction Steps

To 5 ml Dioxane 1.4 g (0.0054 moles) of anhydrous N-2-[2-(methoxy)-phenoxy]-ethyl]-benzylamine, 0.21 g (0.0015 moles) of anhydrous ZnCl2 and 1 g (0.0042 moles) of 4-(oxiranylmethoxy)-9H-carbazole are added and the reaction mixture is heated to 70-75° C. for 2.5 hrs (TLC control for checking conversion to N-benzyl carvedilol). The dioxane is distilled off from the reaction mixture and to the concentrated mass is added 10 ml ethylacetate, followed by 2 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. To this solution of N-benzyl carvedilol in ethylacetate, (0.14 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4.5 Kg/cm2 at temperature of 60-70° C. for a period of about 10 hours. The reaction mixture is filtered and filtrate concentrated to remove ethylacetate. To the resultant syrupy mass n-butanol (2 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (1 ml) and toluene (1 ml) to obtain carvedilol (0.9 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (0.8 g).

Provenance & Evidence