Hydrochloric Acid → HCID 14651684, compound

Participants

Reaction Steps

A solution of 60 g (0.4 mol) of ethyl malonyl chloride in 150 ml of dichloromethane is added over 0.5 hours to a cold (10° C.) solution of 72.76 g (0.4 mol) of L-leucine methyl ester hydrochloride and 86.02 g (0.85 mol) of triethylamine in 1.5 L of dichloromethane with stirring and keeping the temperature at 10° C. during the addition. The solution is allowed to warm to room temperature, stirred another 0.5 hours and poured into 500 ml of water plus ice chips and 80 ml of 1N hydrochloric acid solution. The organic layer is separated and washed successively with 500 ml of cold water, 500 ml of a 2% aqueous solution of sodium bicarbonate and 500 ml of water. The organic layer is separated, dried over magnesium sulfate, charcoaled and filtered. The filtrate is concentrated to afford 101.8 g of (S)-2-[(3-ethoxy-1,3-dioxopropyl)amino]-4-methylpentanoic acid, methyl ester as a viscous oil. Thin layer chromatography (TLC) (ethyl acetate, silica gel, iodine) Rf =0.75. This material is used directly in the next ring closure step.

Provenance & Evidence