Hydrochloric Acid → HCID 15550225, compound

2-Nitro-4-methoxyaniline (16.8 g) was added to water (30 ml) and concentrated hydrochloric acid (160 ml), and stirred at room temperature for 20 minutes and then at 70° C. for 75 minutes. The reaction mixture was cooled with ice and an aqueous solution (30 ml) of sodium nitrite (11.5 g) was dropwise added so that the temperature of the reaction solution did not exceed 5° C. After addition, the mixture was stirred for 1 hour while the temperature was maintained at 10° C. The reaction mixture was filtered and the residue was washed with water (50 ml). The filtrate was cooled with ice, to which an aqueous solution (120 ml) of sodium hydrogencarbonate (123 g) and 1,4-benzoquinone (12.3 g) was dropwise added over 1 hour. After addition, the reaction mixture was stirred for 4 hours while ice cooling and then filtered. The crystal was washed with water and dried. The resulting crystal was dissolved in methanol (200 ml) and acetic acid (20 ml), and 10% palladium/carbon (1.0 g) was added thereto and stirred under a hydrogen atmosphere at room temperature for 3 hours. The reaction mixture was filtered and the residue was washed with methanol (30 ml). Under ice cooling, concentrated aqueous ammonia (50 ml) was dropwise added to the filtrate over 5 minutes. After addition, the mixture was allowed to warm to room temperature and stirred for 12 hours. The reaction mixture was filtered and the crystal was washed with water and dried in vacuo. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=3/1 to 0/1) to yield the titled compound (2.71 g).

1. waitat 70° C. for 75 minutes
2. temperatureThe reaction mixture was cooled with ice
3. customdid not exceed 5° C
4. additionAfter addition
5. stirringthe mixture was stirred for 1 hour while the temperature
6. temperaturewas maintained at 10° C
7. filtrationThe reaction mixture was filtered
8. washthe residue was washed with water (50 ml)
9. temperatureThe filtrate was cooled with ice, to which an aqueous solution (120 ml) of sodium hydrogencarbonate (123 g) and 1,4-benzoquinone (12.3 g)
10. additionwas dropwise added over 1 hour
11. additionAfter addition
12. stirringthe reaction mixture was stirred for 4 hours while ice cooling
13. filtrationfiltered
14. washThe crystal was washed with water
15. customdried
16. dissolutionThe resulting crystal was dissolved in methanol (200 ml)
17. additionacetic acid (20 ml), and 10% palladium/carbon (1.0 g) was added
18. stirringstirred under a hydrogen atmosphere at room temperature for 3 hours
19. filtrationThe reaction mixture was filtered
20. washthe residue was washed with methanol (30 ml)
21. additionUnder ice cooling, concentrated aqueous ammonia (50 ml) was dropwise added to the filtrate over 5 minutes
22. additionAfter addition
23. temperatureto warm to room temperature
24. stirringstirred for 12 hours
25. filtrationThe reaction mixture was filtered
26. washthe crystal was washed with water
27. customdried in vacuo
28. customThe resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=3/1 to 0/1)

ORD record

ord-844a1226404d4ea6bddea5ad430a46fa

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06696573B1