Triethylamine → 7,8-difluoro-3-methyl-2H-1,4-benzoxazine

Participants

Reaction Steps

In a nitrogen stream, a solution of 2.11 ml of t-butyl hypochlorite and 2 ml of ethyl acetate were added dropwise to a mixture of 1.54 g of (R)-(+)-7,8-difluoro-3-methyl-3,4-dihydro-2H-[1,4]benzoxazine (optical purity: 71.7% e.e., (R)), 5.21 ml of triethylamine and 9 ml of ethyl acetate while keeping the internal temperature at -52° C. over a period of about 4 minutes, and the resulting mixture was further stirred at -60° to -50° C. for 30 minutes. The reaction mixture was washed twice with 10 ml portions of 5% aqueous solution of citric acid and further with 10 ml of dilute aqueous ammonia (concentrated aqueous ammonia:water=1:4 (v/v)) and the ethyl acetate layer was dried over anhydrous magnesium sulfate. The ethyl acetate was removed under reduced pressure and the oily residue was purified over silica gel (50 g) column chromatography using chloroform (the bottom layer after shaking with concentrated aqueous ammonia) as the eluent. The solvent was removed from the eluate under reduced pressure to yield 693 mg of 7,8-difluoro-3-methyl-2H-[1,4]benzoxazine as pale yellow crystals (yield: 60.8%).

Provenance & Evidence