Hydrochloric Acid → Methyl 1-benzyl-3-methyl-1H-pyrazole-5-carboxylate

HRID 343130Notes

Reaction equation

HRID 343130 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:6][N:7]=[C:8]([CH3:10])[CH:9]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:7]=[C:8]([CH3:10])[CH:9]=1)=[O:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 178498201HCID 178498201, compound

Product 1

HCID 10263243Methyl 1-benzyl-3-methyl-1H-pyrazole-5-carboxylateYield 26.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 21.91 g (13.63 mmol) of 5-methyl-2H-pyrazole-3-carboxylic acid methyl ester, prepared as in Part A, in 50 mL of DMF is added 2.88 g (20.44 mmol, 1.5 equiv) of K2CO3, followed by 1.95 mL (16.35 mmol, 1.2 equiv) of benzyl bromide. The reaction mixture is stirred 15 min at RT then heated at 50° C. for 20 h. The reaction is cooled to RT, poured into 100 mL 1N HCl, and extracted with Et2O (2×100 mL). The organic layers were washed with H2O (2×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using a gradient elution of hexane/EtOAc 10/1 to 1/1 afforded 833 mg of 2-Benzyl-5-methyl-2H-pyrazole-3-carboxylic acid methyl ester as a yellow oil: 1H NMR (CDCl3, 300 MHz) δ7.42-7.25 (m, 5H), 6.68 (s, 21H), 5.74 (s, 2H), 3.86 (s, 3H), 2.34 (s, 3H).

Workup

  1. temperaturethen heated at 50° C. for 20 h
  2. temperatureThe reaction is cooled to RT
  3. extractionextracted with Et2O (2×100 mL)
  4. washThe organic layers were washed with H2O (2×100 mL)
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customPurification of the crude material by silica gel flash column chromatography
  8. washa gradient elution of hexane/EtOAc 10/1 to 1/1

Sources & evidence

ORD record
ord-b10719e06b304d6c8281bed5994aa448
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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