Toluene → (S)-8-Fluoro-3-methyl-5-nitro-3,4-dihydro-2H-benzo[1,4]oxazine

Participants

Reaction Steps

TFA (3 mL) was added to a solution of [(S)-2-(2,6-difluoro-3-nitrophenoxy)-1-methylethyl]carbamic acid tert-butyl ester (340 mg, 1.02 mmol) in DCM (15 mL) and the mixture was stirred for 90 min at rt. PhMe (25 mL) was added and the solution was concentrated in vacuo. The resultant residue was taken up in MeCN (7 mL); aqueous 2M Na2CO3 (7 mL) was added and the mixture was stirred vigorously for a further 90 min at rt. EtOAc (25 mL) and brine (25 mL) were added and the phases were separated. The aqueous was extracted with EtOAc (2×25 mL), and the combined organics were dried (Na2SO4) and concentrated in vacuo. The crude reaction mixture was purified by flash chromatography (Si—PPC, gradient 0-20% EtOAc in cyclohexane) to afford the title compound as a bright yellow solid (183 mg, 84%). 1H NMR (CDCl3, 300 MHz): δ 7.85 (1H, br s), 7.78 (1H, dd, J=9.8, 5.5 Hz), 6.45 (1H, app. t, J=9.8 Hz), 4.36-4.28 (1H, m), 3.84-3.77 (2H, m), 1.35 (3H, d, J=6.2 Hz)

Provenance & Evidence