Cyanomethylenetributylphosphorane → (9aR)-tert-butyl 3-(2-chloro-3-cyano-4-fluorophenyl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

(3R)-tert-butyl 4-(2-(2-chloro-3-cyano-4-fluorophenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate (15.6 g, 37.3 mmol) and cyanomethylene tri-n-butyl phosphorane (16.4 g, 67.8 mmol) were dissolved in benzene (90 mL), degassed and heated at 100° C. for 16 h. The reaction mixture was concentrated and chromatographed through a 330 g ISCO Redi-sep column and eluted with 35% EtOAc/hexane to yield the title compound (cis-trans diastereomers mixture). LC-MS (IE, m/z): 396 [M+1]+;

Provenance & Evidence