Hydrochloric Acid → Cgp-20712

Participants

Reaction Steps

4.28 ml of 5.9N methanolic hydrochloric acid are added to a solution of 8.39 g of 1-amino-3-[4-(1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl)-phenoxy]-2-propanol in 250 ml of methanol. The pH is adjusted to 8-9 by the addition of solid potassium hydroxide; there are subsequently added 25 g of molecular sieve (pore size 3 Å), 5.6 g of 2,3-dihydro-2,2-dimethyl-7-(2-oxoethoxy)-4H-1,3-benzoxazin-4-one and finally 0.59 g of sodium cyanoborohydride. The mixture, containing the corresponding Schiff's base, is stirred under reflux at room temperature for 18 hours and, after the addition of 50 ml of 5.9N methanolic hydrochloric acid, for a further one hour, filtered and the solvent is removed in a rotary evaporator. The residue is chromatographed on silica gel with a mixture of chloroform/methanol/ammonia (40:50:5), the main fractions are freed of solvent and the residue is recrystallised from methanol, yielding 1-[2-(3 -carbamoyl-4-hydroxyphenoxy)-ethylamino]-3-[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]-phenoxy]-2-propanol having a melting point of 195°-197°.

Provenance & Evidence