Water → 1,3-Dimethyl-5-ethoxycarbonylpyrazole

HRID 915697Notes

Reaction equation

HRID 915697 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:10][N:9]=[C:8]([CH3:11])[CH:7]=1)=[O:5])[CH3:2].[H-].[Na+].O.O1CCC[CH2:16]1>>[CH2:1]([O:3][C:4]([C:6]1[N:10]([CH3:16])[N:9]=[C:8]([CH3:11])[CH:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 4

HCID 962WaterHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 178469061HCID 178469061, compound

Product 1

HCID 1385761,3-Dimethyl-5-ethoxycarbonylpyrazole

Procedure

Dissolve ethyl-3-methylpyrazole-5-carboxylate (1.0893 g, 7.07 mmol) in 10 mL tetrahydrofuran and add it dropwise to a suspension of sodium hydride (60%) (377.6 mg, 9.44 mmol) in 10 mL tetrahydrofuran. After 2 hours, quench the reaction with methyl iodide (excess) and stir for an additional 2 hours. Add water to the reaction and remove the tetrahydrofuran in vacuo. Partition the residue between ethyl acetate and brine. Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to afford 950.0 mg of crude 2,5-dimethyl-2H-pyrazole-3-carboxylic acid ethyl ester. Dissolve this material (950.0 mg, 5.65 mmol) in 10 mL tetrahydrofuran and add it dropwise to a slurry of lithium aluminum hydride (220.2 mg) in 20 mL tetrahydrofuran at 0° C. After 30 minutes at this temperature, heat the reaction to reflux for 2 hours. Cool the reaction to room temperature and add 20 mL ethyl acetate to the reaction. Add 5N sodium hydroxide to the reaction until a white precipitate appears. Filter the reaction and concentrate the filtrate in vacuo. Partition the residue between ethyl acetate and water. Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to afford 493.7 mg of crude (2,5-dimethyl-2H-pyrazol-3-yl)-methanol. Dissolve this crude material (493.7 mg, 3.91 mmol) in 20 mL methylene chloride and add MnO2 (1.2939 g, 14.88 mmol) to the reaction mixture. Heat the reaction mixture to reflux and allow it to stir for 16 hours. Cool the reaction and filter it through a pad of celite. Concentrate the filtrate in vacuo to afford 444.5 mg of crude product. Purify via Biotage chromatography (25% ethyl acetate/Hexanes) to afford 138.7 mg of the title compound 1H NMR (CDCl3) δ 9.81 (1H, s), 6.46 (1H, s), 3.82 (3H, s), 2.24 (3H, s).

Workup

  1. additionadd it
  2. customquench
  3. customthe reaction with methyl iodide (excess)
  4. customremove the tetrahydrofuran in vacuo
  5. customPartition the residue between ethyl acetate and brine
  6. dry with materialDry the organic layer with magnesium sulfate
  7. filtrationFilter
  8. customremove the solvent in vacuo

Sources & evidence

ORD record
ord-4bdee5abbb844f878ac6bca264b14f2c
Source dataset
uspto-grants-2007_09
Patent number
US07265246B2

Reaction notes

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