Diisopropylamine → ethyl 3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

Participants

Reaction Conditions

Reaction Steps

Under nitrogen atmosphere, 52.9 mL (0.37 mol, 3 eq) of diisopropylamine was added to 1.3 liters of THF. 234 mL (0.37 mol, 3 eq) of a 1.6 M solution of n-butyllithium in hexane was added dropwise at −65° C. or lower over 23 minutes. After stirred at −65° C. for 20 minutes, 36.6 mL (0.37 mol, 3 eq) of ethyl acetate was added dropwise at −65° C. or lower over 10 minutes. After stirred at −65° C. for 45 minutes, a solution of 65 g (0.13 mol) of N-methyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamide in 260 mL of THF was added dropwise at −65° C. or lower over 25 minutes. The mixture was stirred at −65° C. for 1 hour, and at −4˜−30° C. for 2 hours. After 370 mL of an aqueous saturated ammonium chloride solution was added dropwise at −20° C. or lower, the mixture was warmed to 30° C. After the layers were separated, the organic layer was washed with 370 mL of an aqueous saturated ammonium chloride solution two times. Concentration under reduced pressure afforded 102 g of ethyl 3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate.

Provenance & Evidence