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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence