L-Glutamine → N-Phthaloyl-L-glutamine

Participants

Reaction Steps

A mixture of deuterium enriched glutamine and sodium carbonate in water is rapidly added N-carbethoxyphthalimide as a solid. After 1 hour, the reaction mixture is filtered to remove unreacted N-carbethoxyphthalimide. The pH of the stirred filtrate is adjusted to 3-4 with 4N HCl. The mixture is then seeded with N-phthaloyl-L-glutamine and the pH adjusted to 1-2 with 4N HCl. The resulting slurry is stirred for 1 hour. The slurry is filtered and the solid washed with water. The solid is dried to afford N-phthaloyl-L-glutamine. N-phthaloyl glutamine, carbonyldiimidazole, and 4-dimethylaminopyridine in anhydrous THF is heated to reflux for 16 hours. The reaction slurry is filtered and the solid washed with methylene chloride. The solid is dried to provide deuterium-enriched thalidomide. Carbon-13 enrichment and nitrogen-15 enrichment of thalidomide may be achieved using similar methods by utilizing the appropriate carbon-13 or nitrogen-15 labeled glutamine starting material.

Provenance & Evidence