Ammonium Chloride → 6-(hydroxy(1-trityl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide

Participants

Reaction Conditions

Reaction Steps

Under nitrogen atmosphere, 5.8 liters of THF was added to 105.6 g (0.40 mol, 1.2 eq) of 6-bromo-N-methyl-2-naphtamide, the mixture was warmed to 50° C. to dissolve it. 500 mL (0.50 mol, 2.4 eq) of a 1.6 M solution of n-butyllithium in hexane was added dropwise at −65° C. or lower over 35 minutes. The mixture was stirred at −65° C. for 1 hour. A solution of 112.7 g (0.33 mol) of 1-trityl-4-formyl-1H-imidazole in 810 mL of THF was added dropwise at −65° C. or lower over 40 minutes. The mixture was stirred at −65° C. for 2 hours. 1.5 Liters of an aqueous saturated ammonium chloride solution was added dropwise at −20° C. or lower, and the mixture was warmed to 30° C. After separation of the layers, the organic layer was washed with 1.5 liters of an aqueous saturated sodium chloride solution two times. After concentration under reduced pressure, 1 liter of ethyl acetate was added to the residue, and the mixture was stirred at 25° C. for 3 hours. Crystals were filtered, and washed with ethyl acetate. Vacuum drying (50° C.) to a constant weight afforded 87.9 g of 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (yield 50%).

Provenance & Evidence