Triethylamine → Phenytoin Impurity 31

Participants

Reaction Steps

5.0 g (17.7 mmol) of 3-(hydroxymethyl)-5,5-diphenylimidazolidine-2,4-dione (hydroxymethylphenytoin) and 7.5 g (74.1 mmol) of triethylamine were dissolved in 30 g of tetrahydrofuran (THF). A solution of 2.4 g (21.0 mmol) of methanesulfonyl chloride in 33.3 g of THF was added at −10 to −5° C. A white suspension formed. The suspension was filtered and the clear filtrate was added to a suspension of 5.8 g (20.8 mmol) of dibenzyl phosphate in 5.0 g of THF at room temperature. After stirring overnight, the mixture was concentrated on a rotary evaporator, 50 g of ethyl acetate and 25 g of water were then added to the residue and the phases were separated. The organic phase was washed once with 20 g of water and then extensively concentrated on a rotary evaporator. 2.5 g of acetone and seed material were added to the residue obtained and the mixture was stirred overnight at 0 to 10° C. The resulting colourless precipitate was filtered off and dried under vacuum. Yield: 6.9 g (72%).

Provenance & Evidence