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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have