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

TFA (3 mL) was added to a solution of [(R)-2-(2,6-difluoro-3-nitrophenoxy)-1-methylethyl]carbamic acid tert-butyl ester (333 mg, 1.00 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 (184 mg, 87%). 1H NMR (CDCl3, 300 MHz): δ 7.84 (1H, br s), 7.79 (1H, dd, J=9.8, 5.6 Hz), 6.45 (1H, app. t, J=9.8 Hz), 4.36-4.28 (1H, m), 3.84-3.76 (2H, m), 1.35 (3H, d, J=6.3 Hz)

1. concentrationthe solution was concentrated in vacuo
2. additionaqueous 2M Na2CO3 (7 mL) was added
3. stirringthe mixture was stirred vigorously for a further 90 min at rt
4. additionEtOAc (25 mL) and brine (25 mL) were added
5. customthe phases were separated
6. extractionThe aqueous was extracted with EtOAc (2×25 mL)
7. dry with materialthe combined organics were dried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customThe crude reaction mixture
10. customwas purified by flash chromatography (Si—PPC, gradient 0-20% EtOAc in cyclohexane)

ORD record

ord-5444556ee5b14c4ea8cdc1e74798d412

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2