Formic Acid → Benzenamine, 5-methoxy-N-methyl-2-nitro-

Temperature

60 °C

A mixture of formic acid (7.64 g) and acetic anhydride (16.9 g) was stirred at 60° C. for 2 hr then a solution (100 mL) of 5-methoxy-2-nitroaniline (9.30 g) in tetrahydrofuran was added dropwise, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate. The solution was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. To a solution (200 mL) of the residue in tetrahydrofuran was added a 1.0M solution (140 mL) of borane-tetrahydrofuran complex in tetrahydrofuran at 0° C., and the mixture was stirred with heating under reflux for 2 hr. Methanol was added to the reaction mixture at 0° C., and the mixture was stirred at room temperature for 30 min. After stirring, 1N hydrochloric acid was added to adjust to pH=2. The reaction mixture was stirred with heating under reflux for 1 hr, and concentrated under reduced pressure, and the residue was dissolved in ethyl acetate. The solution was washed with water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure to give the title object compound (6.30 g, 62%) as a colorless oil.

1. stirringthe mixture was stirred overnight at room temperature
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. dissolutionthe residue was dissolved in ethyl acetate
4. washThe solution was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. additionTo a solution (200 mL) of the residue in tetrahydrofuran was added a 1.0M solution (140 mL) of borane-tetrahydrofuran complex in tetrahydrofuran at 0° C.
8. stirringthe mixture was stirred
9. temperaturewith heating
10. temperatureunder reflux for 2 hr
11. additionMethanol was added to the reaction mixture at 0° C.
12. stirringthe mixture was stirred at room temperature for 30 min
13. stirringAfter stirring
14. addition1N hydrochloric acid was added
15. stirringThe reaction mixture was stirred
16. temperaturewith heating
17. temperatureunder reflux for 1 hr
18. concentrationconcentrated under reduced pressure
19. dissolutionthe residue was dissolved in ethyl acetate
20. washThe solution was washed with water and saturated brine
21. dry with materialdried over sodium sulfate
22. concentrationconcentrated under reduced pressure

ORD record

ord-c2e1bf5fc4eb4c93a07fd237407aa8a8

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436043B2