Acetic Acid → 7-amino-4-(2-methoxy-4-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazin-3(4H)-one

Temperatur

70 °C

4-(2-Methoxy-4-(trifluoromethyl)phenyl)-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one (2.1 g, 5.70 mmol) was dissolved in THF (22.81 ml) and acetic acid (17.95 ml, 314 mmol) in a 250 mL rbf, and iron (3.18 g, 57.0 mmol) was added. The flask was sealed and heated to 70° C. for 1 hr until the reaction was complete by LCMS. The reaction was cooled to RT, diluted with THF (50 mL), and filtered through Celite, washing well with 200 mL of THF. The filtrate was concentrated via rotary evaporation, and partitioned between sat. aq. sodium bicarbonate solution (50 mL) and EtOAc (50 mL). The layers were separated, and the aqueous was then extracted two times with EtOAc (2×50 mL). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated to a brown oil. The oil was loaded onto a silica column and purified by MPLC with a gradient Heptanes:EtOAc column (0-100%). Fractions were combined and concentrated to give 7-amino-4-(2-methoxy-4-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (1.434 g, 4.24 mmol, 74.3% yield) as an off-white foamy solid.

1. customThe flask was sealed
2. temperatureThe reaction was cooled to RT
3. filtrationfiltered through Celite
4. washwashing well with 200 mL of THF
5. concentrationThe filtrate was concentrated via rotary evaporation
6. custompartitioned between sat. aq. sodium bicarbonate solution (50 mL) and EtOAc (50 mL)
7. customThe layers were separated
8. extractionthe aqueous was then extracted two times with EtOAc (2×50 mL)
9. washThe combined organics were washed with brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated to a brown oil
13. custompurified by MPLC with a gradient Heptanes
14. concentrationconcentrated

ORD-Eintrag

ord-01fc92bf7d514e92b59c6c920f1feef6

Quelldatensatz

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09346798B2