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

Participants

Reaction Conditions

Reaction Steps

tert-Butyl (3S)-4-[2-(3-cyano-2,4-difluorophenyl)-2-hydroxyethyl]-3-(hydroxymethyl)piperazine-1-carboxylate (1.2 g, 3.0 mmol) and cyanomethylenetri-n-butylphosphorane (1.31 g, 5.44 mmol) were dissolved in 5 mL of benzene. The reaction mixture was degassed and heated to 100° C. for 16 h. LC-MS analysis showed product peak at 2.07 min (M+1=380). The reaction was cooled and evaporated to dryness. The residue was purified by MPLC chromatography through an 80 g Redi-sep column eluting with a 40% EtOAc/60% hexane mixture to yield a cis-trans mixture of the title compound.

Provenance & Evidence