Citric Acid → Diisopropyl ethylmalate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of diisopropylamine (19.69 ml., 140 mmole) in 200 ml. of dry THF maintained under nitrogen at 0° C. was added with stirring n-butyl lithium (86.68 ml., 134.37 mmole). After 10 minutes the solution was cooled to about -50° C. and a solution of diisopropyl malate (13.95 g., 63.99 mmole) prepared with D-malic acid in dry hexamethylphosphoramide, HMPA (11.45 ml., 63.99 mmole) was added. The resulting red solution was allowed to warm to a temperature of about -10° C., and after a few minutes the mixture was cooled to about -20° C. and ethyl iodide (6.14 ml., 76.88 mmole) was added. The reaction mixture was allowed to warm to room temperature over one hour and was then heated for 45 minutes at 45° C. The reaction mixture was allowed to cool to room temperature, was neutralized with 1M citric acid, and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, filtered, and evaporated to dryness to yield 15.5 g. (62.99 mmole, 98.5% yield) of diisopropyl ethylmalate as an oil. The product was obtained as a mixture of the diastereoisomers represented by the following formulas ##STR90##

Provenance & Evidence