Hydrochloric Acid → HCID 15550225, compound

Temperature

70 °C

2-Nitro-4-methoxyaniline (16.8 g) was added to water (30 mL) and concentrated hydrochloric acid (160 mL). The mixture was stirred at room temperature for 20 minutes and further at 70° C. for 75 minutes. An aqueous solution (30 mL) containing sodium nitrite (11.5 g) was added dropwise to the reaction solution while the reaction solution was maintained at a temperature of 5° C. or less by ice cooling. After the adding was completed, the reaction solution was stirred for 1 hour while maintained at 10° C. The reaction solution was filtered and the residue was washed with water (50 mL). The filtrate was cooled with ice, to which a mixed aqueous solution (120 mL) of sodium hydrogencarbonate (123 g) and 1,4-benzoquinone (12.3 g) was added dropwise over 1 hour. After the adding was completed, the reaction solution was stirred for 4 hours with ice cooling and then filtered. The thus obtained crystal was washed with water, dried, and then dissolved in methanol (200 mL) and acetic acid (20 mL). 10% Palladium/carbon (1.0 g) was added to the mixture, which was stirred under a hydrogen atmosphere at room temperature for 3 hours. The reaction solution was filtered and the residue was washed with methanol (30 mL). Concentrated aqueous ammonia (50 mL) was added dropwise to the filtrate with ice cooling over 5 minutes. After the adding was completed, the reaction solution was allowed to warm to room temperature and stirred for 12 hours. The reaction solution was filtered and the crystal was washed with water and then dried under reduced pressure. The thus obtained crude product was purified by silica gel column chromatography (eluent: 3:1 to 0:1 hexane/ethyl acetate) to give the title compound (2.71 g).

1. additionwas added dropwise to the reaction solution while the reaction solution
2. temperaturewas maintained at a temperature of 5° C. or less by ice cooling
3. stirringthe reaction solution was stirred for 1 hour
4. temperaturewhile maintained at 10° C
5. filtrationThe reaction solution was filtered
6. washthe residue was washed with water (50 mL)
7. temperatureThe filtrate was cooled with ice, to which a mixed aqueous solution (120 mL) of sodium hydrogencarbonate (123 g) and 1,4-benzoquinone (12.3 g)
8. additionwas added dropwise over 1 hour
9. stirringthe reaction solution was stirred for 4 hours with ice cooling
10. filtrationfiltered
11. washThe thus obtained crystal was washed with water
12. customdried
13. dissolutiondissolved in methanol (200 mL)
14. addition10% Palladium/carbon (1.0 g) was added to the mixture, which
15. stirringwas stirred under a hydrogen atmosphere at room temperature for 3 hours
16. filtrationThe reaction solution was filtered
17. washthe residue was washed with methanol (30 mL)
18. additionConcentrated aqueous ammonia (50 mL) was added dropwise to the filtrate with ice cooling over 5 minutes
19. temperatureto warm to room temperature
20. stirringstirred for 12 hours
21. filtrationThe reaction solution was filtered
22. washthe crystal was washed with water
23. customdried under reduced pressure
24. customThe thus obtained crude product
25. customwas purified by silica gel column chromatography (eluent: 3:1 to 0:1 hexane/ethyl acetate)

ORD record

ord-02d7a4ffc63044ba8dd5b3b35c57c261

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06495701B1