Water → HCID 67136016, compound

5-(2,6-Difluoro-4-nitrophenoxy)-1,3-dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazole (i.e. the product of Synthesis Example 8) (0.780 g, 1.95 mmol) was combined with iron powder (325 mesh, 0.58 g, 10 mmol) and ammonium chloride (64 mg, 1.2 mmol) in ethanol (27 mL) to which water (3 mL) had been added. The mixture was heated at reflux for 1.25 h and then allowed to cool. The reaction mixture was diluted with an equal volume of ethyl acetate and filtered through Celite filter aid. The filtrate was dried with MgSO4 and concentrated. Analysis by LC/MS showed the major component (93%) to have mass 370 amu (AP+). The residue was dissolved in anhydrous dimethyl sulfoxide (8 mL), and a commercial solution of sodium methoxide in methanol (0.45 mL of 25% solution) was added. This solution was stirred under nitrogen and heated at reflux for 1 h. Additional sodium methoxide/methanol solution (0.20 mL) was added, and heating was continued for an additional 30 minutes. The reaction mixture was allowed to cool, and it was then treated with aqueous citric acid solution (1 M, 5 mL), diluted with water (50 mL) and extracted with ethyl acetate (2×25 mL). The organic phase was washed with water (3×) and with brine, dried over MgSO4, and concentrated to leave the title product, a compound of the present invention, as a viscous oil (0.52 g).

1. additionhad been added
2. temperatureThe mixture was heated
3. temperatureat reflux for 1.25 h
4. temperatureto cool
5. filtrationfiltered through Celite
6. filtrationfilter aid
7. dry with materialThe filtrate was dried with MgSO4
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in anhydrous dimethyl sulfoxide (8 mL)
10. additiona commercial solution of sodium methoxide in methanol (0.45 mL of 25% solution) was added
11. temperatureheated
12. temperatureat reflux for 1 h
13. additionAdditional sodium methoxide/methanol solution (0.20 mL) was added
14. temperatureheating
15. temperatureto cool
16. additionit was then treated with aqueous citric acid solution (1 M, 5 mL)
17. additiondiluted with water (50 mL)
18. extractionextracted with ethyl acetate (2×25 mL)
19. washThe organic phase was washed with water (3×) and with brine
20. dry with materialdried over MgSO4
21. concentrationconcentrated

ORD record

ord-3c0ea8d5ccb447008c7a10595c6be8c1

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062005B2