Methyl iodide → ethyl 1-(4-ethoxy-2,6-difluorobenzyl)-5-methoxy-4-methyl-1H-pyrazole-3-carboxylate

HRID 1774517Notes

Reaction equation

HRID 1774517 reaction equation
[CH2:1]([O:3][C:4]1[CH:22]=[C:21]([F:23])[C:7]([CH2:8][N:9]2[C:13]([OH:14])=[C:12]([CH3:15])[C:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:10]2)=[C:6]([F:24])[CH:5]=1)[CH3:2].IC.[C:27](=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([F:24])[C:7]([CH2:8][N:9]2[C:13]([O:14][CH3:27])=[C:12]([CH3:15])[C:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:10]2)=[C:21]([F:23])[CH:22]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 11430Potassium CarbonateHCID 178470463HCID 178470463, compound

Product 1

HCID 89662186ethyl 1-(4-ethoxy-2,6-difluorobenzyl)-5-methoxy-4-methyl-1H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

3.95 g of ethyl 1-(4-ethoxy-2,6-difluorobenzyl)-5-hydroxy-4-methyl-1H-pyrazole-3-carboxylate 1-1-1 (11.6 mmol, 1.0 eq.) were dissolved in 50 mL of acetone. 1.45 mL of iodomethane (23.2 mmol, 2.0 eq.) and 5.78 g (41.8 mmol, 3.6 eq.) of potassium carbonate were added and stirred over for 24 hours at rt. 1.45 mL of iodomethane (23.2 mmol, 2.0 eq.) were added and the mixture was stirred for further 24 hours at rt. The suspension was filtered off over sea sand and the filtrate was concentrated in vacuo. The residue was extracted by DCM and water. The aqueous layer was extracted twice with DCM. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography to give 2.29 g (6.46 mmol, 55.7%) of analytically pure target compound.

Workup

  1. stirringthe mixture was stirred for further 24 hours at rt
  2. filtrationThe suspension was filtered off over sea sand
  3. concentrationthe filtrate was concentrated in vacuo
  4. extractionThe residue was extracted by DCM and water
  5. extractionThe aqueous layer was extracted twice with DCM
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography
  9. customto give 2.29 g (6.46 mmol, 55.7%) of analytically pure target compound

Sources & evidence

ORD record
ord-ec0eb5c6110d4911a107def9dccbfb63
Source dataset
uspto-grants-2016_02
Patent number
US09260412B2

Reaction notes

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