Dicyclohexylcarbodiimide → (4R)-3-Benzoyl-4-[(R)-alpha-methyl-p-hydroxybenzylcarbamoyl]-1,1-dioxothiazolidine

Participants

Reaction Conditions

Reaction Steps

1.00 g (7.29 mmole) of (R)-α-methyl-p-hydroxybenzylamine (prepared as described in Preparation 13), 1.12 g (7.29 mmole) of N-hydroxybenzotriazole monohydrate and 1.51 g (7.29 mmole) of dicyclohexylcarbodiimide were added in that order to a solution of 1.96 g (7.29 mmole) of (4R)-3-benzoyl-1,1-dioxothiazolidine-4-carboxylic acid (prepared as described in Preparation 12) in 100 ml of dimethylformamide cooled at 5° C., and then the mixture was stirred at a temperature between 3° and 6° C. for 30 minutes and then at room temperature for a further 23 hours. The reaction mixture was filtered, the insolubles were washed with 20 ml of ethyl acetate, and the filtrate and the washings were combined. 50 ml of ethyl acetate were added to the combined mixture, which was washed twice, each time with 50 ml of a 4% w/v aqueous solution of sodium bicarbonate, and the organic phase was separated and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by Lobar column chromatography through silica gel (Merck, Art-10402), eluted with a 2:1 by volume mixture of ethyl acetate and cyclohexane. The eluate was concentrated by evaporation under reduced pressure and the residue was lyophilized with a mixture of acetone and benzene to give 2.04 g (72.0%) of the title compound in the form of a colorless powder.

Provenance & Evidence