Sodium hydride → Ethyl 1-(2-(2,5-dimethoxyphenyl)-2-oxoethyl)-3-(pyridin-3-yl)-1H-pyrazole-5-carboxylate

HRID 1409977Notes

Reaction equation

HRID 1409977 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:11]=[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH:9][N:8]=2)[CH:2]=1.[H-].[Na+].Br[CH2:20][C:21]([C:23]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:24]=1[O:31][CH3:32])=[O:22]>>[CH3:32][O:31][C:24]1[CH:25]=[CH:26][C:27]([O:29][CH3:30])=[CH:28][C:23]=1[C:21](=[O:22])[CH2:20][N:9]1[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:11][C:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[N:8]1

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 709972-Bromo-2',5'-dimethoxyacetophenoneHCID 575603Ethyl 3-(pyridin-3-yl)-1H-pyrazole-5-carboxylate

Product 1

HCID 86267540Ethyl 1-(2-(2,5-dimethoxyphenyl)-2-oxoethyl)-3-(pyridin-3-yl)-1H-pyrazole-5-carboxylate

Procedure

To a flame dried flask equipped with a stirbar cooled under argon was added ethyl 3-(pyridin-3-yl)-1H-pyrazole-5-carboxylate (0.02 grams, 0.092 mmol, 0.1 M in THF). While stirring at room temperature NaH (0.0055 grams, 1.8 mmol, 60% in mineral oil, purchase from Aldrich) was added. After fifteen minutes 2-bromo-1-(2,5-dimethoxyphenyl)ethanone (0.047 grams, 0.14 mmol, purchased from Aldrich) was added as a solid. The reaction was stirred overnight. The next day, the reaction was quenched with 0.1M HCl and the organic material extracted using ethyl acetate. The aqueous layer was salted out using sodium chloride and washed twice with ethyl acetate. The combined organic material was then dried with sodium sulfate, filtered, and concentrated. Purification was done on preparative thin layer chromatography using hexanes/ethyl acetate (1:2) to afford the desired compound. Yield, 10%. 1H-NMR δ9.07 (bs, 1H), 8.58 (bs, 1H), 8.13 (d, 1H), 7.47 (d, 1H), 7.31 (bs, 1H), 7.29 (s, 1H), 7.14 (dd, 1H), 7.00 (d, 1H), 6.03 (s, 2H), 4.32 (q, 2H), 3.99 (s, 3H), 3.79 (s, 3H), 1.35 (t, 3H). Calculated mass for C21H21N3O5, 395.15, observed, 396.3 (M+1).

Workup

  1. customTo a flame dried flask
  2. customequipped with a stirbar
  3. temperaturecooled under argon
  4. additionwas added
  5. customThe next day, the reaction was quenched with 0.1M HCl
  6. extractionthe organic material extracted
  7. washwashed twice with ethyl acetate
  8. dry with materialThe combined organic material was then dried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification

Sources & evidence

ORD record
ord-53bf67c2957c49bca34399771854159f
Source dataset
uspto-grants-2014_12
Patent number
US08921401B2

Reaction notes

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