Sodium hydride → 1-(2-methoxyethyl)-3,5-dimethyl-1H-pyrazole-4-carboxylic acid

HRID 1685056Notes

Reaction equation

HRID 1685056 reaction equation
[H-].[Na+].[CH3:3][C:4]1[C:8]([C:9]([O:11]CC)=[O:10])=[C:7]([CH3:14])[NH:6][N:5]=1.[H][H].Br[CH2:18][CH2:19][O:20][CH3:21]>C1COCC1>[CH3:21][O:20][CH2:19][CH2:18][N:6]1[C:7]([CH3:14])=[C:8]([C:9]([OH:11])=[O:10])[C:4]([CH3:3])=[N:5]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 215436ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 435653931-(2-methoxyethyl)-3,5-dimethyl-1H-pyrazole-4-carboxylic acidYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60%, 120 mg, 3.0 mmol) was suspended in THF (2 ml) at 0 C. Ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylate (168 mg, 1.0 mmol) dissolved in THF (2 mL) was added drop-wise. Stirring was maintained until the evolution of hydrogen stopped. 1-Bromo-2-methoxyethane (208 mg, 1.5 mmol) was added and the reaction was heated at reflux at 70 C for 48 hours. Reaction was quenched with water at 0 C, acidified to pH=1-2 with HCl (2M) and was extracted with EtOAc. The organic layer was washed with water, NH4Cl aq., and brine, and dried with Na2SO4, and concentrated. The residue was subjected to HPLC purification. White solid (67 mg, 0.34 mmol, 34%) was obtained after stripping of solvents and drying. ESI-MS m/z 199.4 (M+H).

Workup

  1. additionwas added drop-wise
  2. temperaturethe reaction was heated
  3. temperatureat reflux at 70 C for 48 hours
  4. customReaction
  5. customwas quenched with water at 0 C
  6. extractionwas extracted with EtOAc
  7. washThe organic layer was washed with water, NH4Cl aq., and brine
  8. dry with materialdried with Na2SO4
  9. concentrationconcentrated
  10. customThe residue was subjected to HPLC purification

Sources & evidence

ORD record
ord-43890c2bbdca4528a84345f0a44e6467
Source dataset
uspto-grants-2012_04
Patent number
US08148380B2

Reaction notes

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