Sommelet-Hauser rearrangement of an ammonium ylide derived from the HIV-1 reverse transcriptase inhibitor nevirapine

Article abstract of DOI:10.1002/jhet.5570320604

Functionalization at the 3-position of the dipyridodiazepinone nevirapine (1) has been accomplished by Sommelet-Hauser rearrangement of an ylide derived from 1. Treatment of N-cyanomethylpyrrolidinium salt 4 with potassium tert-butoxide in a mixture of dimethylsulfoxide and tetrahydrofuran at -10°, followed by acid hydrolysis, afforded a mixture of compounds 5 and 6 in a ratio of 1:1.8. Upon treatment of 4 with sodium amide in liquid ammonia, 5 and 6 were obtained in a ratio of 1.5:1 and a combined yield of 83%. Compound 5 is the desired product resulting from Sommelet-Hauser rearrangement of 4, whereas 6 derives from competing Stevens rearrangement and intramolecular cyclization of the aldehyde produced upon hydrolysis. Baeyer-Villiger oxidation of 5 afforded the 3-hydroxy derivative 2, a recently identified metabolite of nevirapine.