In structure-activity relationship studies directed toward the use of mGluR5 antagonists in the treatment of drug abuse, we sought a convenient means for gaining access to the oxazole analogues of MTEP. Toward this end, the aldehyde group in 2-methyloxazole-4-carboxaldehyde was successfully converted to a trimethylsilylethynyl group via the preparation of a dibromoolefin, conversion to acetylide using NaHMDS and MeLi, and trapping with TMSCl. The resulting versatile intermediate, 2-methyl-4-[(trimethylsilyl)ethynyl]oxazole, was subjected to a modified Sonogashira coupling reaction involving an in situ desilylation reaction with Bu4NF and palladium-catalyzed coupling with an aryl or heteroaryl iodide to give the desired oxazole analogues.
ASJC Scopus subject areas
- Organic Chemistry