Diisopropylamine → Ethyl 3-hydroxy-3-(1-trityl-1h-imidazol-4-yl)propanoate

Participants

Reaction Conditions

Reaction Steps

Diisopropylamine (33.8 ml) was dissolved in dry THF (445 ml) under an argon atmosphere. A solution (1.6 M; 150 ml) of n-butyl lithium in hexane was added at not more than 0° C. with stirring under ice-cooling (ice-salt), and the mixture was stirred for 30 min. The mixture was then cooled to −70° C. in a dry ice-acetone bath and ethyl acetate (23.5 ml)/dry THF (60 ml) solution was added at not more than −65° C. The mixture was stood with stirring for 1 h 20 min. The reaction mixture was added to a solution (1185 ml) cooled to −70° C. of 1-trityl-4-formyl-1H-imidazole (67.7 g) in dry THF at not more than −60° C., and the mixture was stirred for 1 h. A 20% aqueous ammonium chloride solution (445 ml) was added to stop the reaction and the mixture was allowed to warm to room temperature over 1 h. An equivalent amount of water was added and the mixture was partitioned. The aqueous layer was extracted with ethyl acetate. The organic layer was combined and the mixture was dried over anhydrous sodium sulfate. The solvent was evaporated, and the precipitated crystals were finely divided with hexane, collected by filtration and dried to give the title compound (77.26 g) as colorless crystals.

Provenance & Evidence