Dimethyl oxalate → HCID 22315365, compound

HRID 1292304Notes

Reaction equation

HRID 1292304 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[C:8]([F:10])[C:7]([O:11][CH3:12])=[C:6]([F:13])[CH:5]=1)=[O:3].[C:14](OC)(=[O:19])[C:15]([O:17][CH3:18])=[O:16].C[O-].[Na+]>CO.C(Cl)Cl>[F:13][C:6]1[CH:5]=[C:4]([C:2](=[O:3])[CH2:1][C:14](=[O:19])[C:15]([O:17][CH3:18])=[O:16])[CH:9]=[C:8]([F:10])[C:7]=1[O:11][CH3:12]

Participants

6

Reactant 3

HCID 11120Dimethyl oxalateHCID 27369833',5'-Difluoro-4'-methoxyacetophenoneHCID 10942334Sodium Methoxide

Product 1

HCID 22315365HCID 22315365, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3,5-difluoro-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)-1H-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 C17H13 F2N3O3S: C, 51.06; H, 3.57; N, 9.92. Found: C, 51.06; H, 3.54, N, 9.99.

Workup

  1. customThe crude reaction
  2. washwashed with potassium bisulfate (0.1N solution), brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8493080f231d4de388cdfcf1750d41c4
Source dataset
uspto-grants-1998_05
Patent number
US05756529

Reaction notes

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