Methylhydrazine → 3-(Difluoromethyl)-1-methyl-1H-pyrazole

At 22° C., a solution of 45 g of an 85.6% strength mixture comprising 1,1-difluoro-4-ethoxy-3-buten-2-one (0.164 mol) and 1,1-difluoro-4,4-diethoxy-2-butanone (0.071 mol) in a ratio of 2.3/1 in acetic acid (30 ml) was added dropwise over a period of 37 min to a solution of methylhydrazine (99% pure, 11.9 g, 0.258 mol) in acetic acid (460 ml). The resulting reaction solution was stirred at 22° C. for 19 h. The acetic acid was then removed under reduced pressure (43° C./30 mbar). The oily residue was taken up in methyl tert-butyl ether (MTBE, 300 ml) and washed with water (250 ml). The aqueous phase was extracted once with MTBE (150 ml). The collected organic solutions were dried over sodium sulfate, filtered and freed from the solvent under reduced pressure (40° C./400 to 30 mbar). The residue (23.5 g) was subjected to fractional distillation to isolate the product. The main fraction (21.5 g; transition temperature 52° C. at 22 mbar) contained 3-difluoro-N-methylpyrazole and 5-difluoro-N-methylpyrazole in a ratio of 2.6:1 (GC retention times: 5-isomer: 7.6 min; 3-isomer: 9.2 min). Taking into account the amounts of product found in the minor fractions and the cold traps, the yield is 75.5% (sum of both isomers).

1. customThe resulting reaction solution
2. customThe acetic acid was then removed under reduced pressure (43° C./30 mbar)
3. washwashed with water (250 ml)
4. extractionThe aqueous phase was extracted once with MTBE (150 ml)
5. dry with materialThe collected organic solutions were dried over sodium sulfate
6. filtrationfiltered
7. customfreed from the solvent under reduced pressure (40° C./400 to 30 mbar)
8. distillationThe residue (23.5 g) was subjected to fractional distillation
9. customto isolate the product
10. customThe main fraction (21.5 g; transition temperature 52° C. at 22 mbar)
11. customin a ratio of 2.6:1 (GC retention times: 5-isomer: 7.6 min; 3-isomer: 9.2 min)

ORDレコード

ord-96ec873831ad427fb59a4b76e9bae77b

出典データセット

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08153820B2