Sommelet‐hauser rearrangement of an ammonium ylide derived from the HIV‐1 reverse transcriptase inhibitor nevirapine

Abstract

AbstractFunctionalization 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.