Methylhydrazine → ethyl 5-(2,6-difluorophenyl)-1-methyl-1H-pyrazole-3-carboxylate

To a mixture of 2,6-difluoroacetophenone (4.7 g, 0.03 mol) and 1,2-diethyl ethanedioate (4.8 g, 0.033 mol) in ethanol (33 mL) was added sodium tert-butoxide (3.17 g, 0.033 mol). After 1 h, more ethanol (30 mL) was added to the reaction mixture and stirring was continued for 1 h. The reaction mixture was partitioned between hydrochloric acid (1 N) and diethyl ether. The organic phase was separated, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to half its original volume. To the resulting mixture was added methylhydrazine (1.52 g, 0.033 mol) and stirring was continued overnight. The reaction mixture was concentrated under reduced pressure and the resulting material was purified by silica gel chromatography (5 to 20% gradient of ethyl acetate in methylene chloride as eluant) to provide the title compound as a solid (1.0 g).

1. waitwas continued for 1 h
2. customThe reaction mixture was partitioned between hydrochloric acid (1 N) and diethyl ether
3. customThe organic phase was separated
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure to half its original volume
7. stirringstirring
8. waitwas continued overnight
9. concentrationThe reaction mixture was concentrated under reduced pressure
10. customthe resulting material was purified by silica gel chromatography (5 to 20% gradient of ethyl acetate in methylene chloride as eluant)

ORD-Eintrag

ord-346fa9d45dff41edac41bda2c0541f34

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08754115B2