Triethylamine → HCID 178445513, compound

Participants

Reaction Steps

A mixture of 13.47 g of ethyl hydrogen 2-[(R)-(acetamido)(hydroxyphosphinyl)methyl]-2(RS)-isobutylmalonate and 8.42 g of triethylamine in 420 ml of dry toluene was heated under reflux for 2 hours. After cooling, the solvent was removed by evaporation and the residue was dissolved in a mixture of 96 ml of water and 144 ml of concentrated hydrochloric acid and the solution was heated under reflux for 4 hours under a nitrogen atmosphere. The solution was evaporated to dryness and the 2-[(R)-(amino)(hydroxyphosphinyl)methyl]-4-methylvaleric acid obtained was dissolved in 225 ml of aqueous saturated sodium hydrogen carbonate solution and 45 ml of tetrahydrofuran. 30 g of solid sodium hydrogen carbonate and 45 ml of benzyl chloroformate were added and the mixture was stirred at room temperature for 48 hours in a nitrogen atmosphere. The solution was extracted twice with diethyl ether and the aqueous solution was acidified by the careful addition of hydrochloric acid and then extracted five times with dichloromethane containing 10% methanol. The extracts were dried over magnesium sulfate and evaporated to give a colorless gum which was crystallized from ethyl acetate. There were obtained 7.0 g of 2(R or S)-[(R)-benzyl-oxyformamido)(hydroxyphosphinyl)methyl]-4-methylvaleric acid as a single diasteroisomer in the form of a white solid; MS: 344 (M+H)+.

Provenance & Evidence