반응 #2028873

ord-be6a99d64d3143e1bb8b649e372cc67c

반응 방정식

COc1c(F)cc(C(C)=O)cc1F
3,5-fluoro-4-methoxyacetophenone
COc1c(F)cc(C(C)=O)cc1F
3,5-difluoro-4-methoxyacetophenone
COC(=O)C(=O)OC
dimethyl oxalate
C[O-].[Na+]
sodium methoxide
COC(=O)C(=O)CC(=O)c1cc(F)c(OC)c(F)c1
methyl 4-(3,5-difluoro-4-methoxyphenyl)-2,4-dioxo-butanoate

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타The crude reaction
  2. 2
    세척washed with potassium bisulfate (0.1N solution), brine
  3. 3
    건조dried over MgSO4
  4. 4
    여과filtered
  5. 5
    농축concentrated in vacuo

실험 절차

To a stirred solution of 3,5-fluoro-4-methoxyacetophenone from Step 1 (6.46 g, 34.70 mmol) and dimethyl oxalate (6.15 g, 52.05 mmol) in methanol (80 mL), was added sodium methoxide solution (13.4 mL of 25% solution, 58.99 mmol) in one portion and the reaction stirred overnight. The crude reaction was diluted with methylene chloride, washed with potassium bisulfate (0.1N solution), brine, dried over MgSO4, filtered, and concentrated in vacuo yielding methyl 4-(3,5-difluoro-4-methoxyphenyl)-2,4-dioxo-butanoate as an off white crystalline solid which was used as is. A mixture of 4-(3,5-difluoro-4-methoxyphenyl)-2,4-dioxo-butanoate and 4-sulfonamidophenylhydrazine hydrochloride salt (7.76 g, 34.70 mmol) dissolved in methanol was warmed to reflux for 9 hours. Upon allowing the clear reaction to cool to room temperature, a crystalline precipitate formed which was collected by vacuum filtration yielding 5.45 g, (37% based upon the 3,5-difluoro-4-methoxyacetophenone) of methyl 1-(4-aminosulfonylphenyl)-5-(3,5-difluoro-4-methoxyphenyl)-1-H-pyrazole-3-carboxylate as an off-white solid: mp 185°-190° C.; 1H NMR (CDCl3/300 mHz) 7.95 (d, J=8.86, 2H), 7.49 (d, J=8.86, 2H), 7.02 (s, 1H), 6.77 (m, 2H), 4.99 (s, 2H, 4.04 (s, 3H), 3.98 (s, 3H); 19F NMR (CDCl3/300 mHz) −126.66. Anal. Calc'd for C17H13F2N3O3S: C, 51.06; H, 3.57; N, 9.92. Found: C, 51.06; H, 3.54, N, 9.99.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: USRE044048E1uspto-grants-2013_03