Hydrochloric Acid → HCID 67131937, compound

Temperature

0 °C

4-Fluoro-2-methoxybenzaldehyde (Fluorochem, 4.5 g) was dissolved in methanol (40 ml) and cooled to 0° C. Sodium borohydride (1.1 g) was added and the mixture was stirred for 1 hour. Water (200 ml) was added and the mixture was concentrated under reduced pressure (ca. 100 ml). The resulting precipitate was isolated by filtration, washed with water and dried under vacuum and gave 4-fluoro-2-methoxy-phenyl)-methanol (3.76 g). This alcohol (3.76 g) was dissolved in THF (100 ml) and N-Hydroxyphthalimide (3.93 g) and triphenylphosphine (6.32 g) was added followed by drop-wise addition of diisopropyl azodicarboxylate (4.87 g). The resulting turbid red reaction mixture was stirred at room temperature for 30 min. The mixture was filtrated through a pad of silica gel and the filtrate was evaporated under reduced pressure. Ethanol (70 ml) was added to the residue which dissolved on heating. On cooling a crystalline material formed that was isolated by filtration and dried under vacuum. This phthalimide intermediate (6.15 g) was suspended in ethanol (50 ml) and hydrazine monohydrate (1.0 ml) dissolved in ethanol (10 ml) was added. The reaction mixture was heated to reflux and stirred for ca. 3 hours. The mixture was cooled to room temperature and the solid material was removed by filtration. The filtrate was evaporated under reduced pressure and the residue was treated with EtOAc and filtrated. 4 M HCl in dioxane (1.0 eq.) was added to the filtrate and the resulting precipitated material was isolated by filtration and gave the title compound (3.26 g) as a white solid material. 13C-NMR (DMSO-d6) δ 163.7, 159.2, 132.6, 117.8, 106.6, 99.7, 70.2, 56.0.

1. concentrationthe mixture was concentrated under reduced pressure (ca. 100 ml)
2. customThe resulting precipitate was isolated by filtration
3. washwashed with water
4. customdried under vacuum
5. customgave 4-fluoro-2-methoxy-phenyl)-methanol (3.76 g)
6. customThe resulting turbid red reaction mixture
7. stirringwas stirred at room temperature for 30 min
8. filtrationThe mixture was filtrated through a pad of silica gel
9. customthe filtrate was evaporated under reduced pressure
10. additionEthanol (70 ml) was added to the residue which
11. dissolutiondissolved
12. temperatureon heating
13. temperatureOn cooling a crystalline material
14. customformed
15. customthat was isolated by filtration
16. customdried under vacuum
17. dissolutionhydrazine monohydrate (1.0 ml) dissolved in ethanol (10 ml)
18. additionwas added
19. temperatureThe reaction mixture was heated
20. temperatureto reflux
21. stirringstirred for ca. 3 hours
22. temperatureThe mixture was cooled to room temperature
23. customthe solid material was removed by filtration
24. customThe filtrate was evaporated under reduced pressure
25. additionthe residue was treated with EtOAc
26. filtrationfiltrated
27. customthe resulting precipitated material
28. customwas isolated by filtration

ORD record

ord-f33f734bb12f45f78a7269a26301c59d

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08034811B2