Water → ethyl 5-cyclopropyl-1-(4-ethoxy-2,6-difluorobenzyl)-4-methyl-1H-pyrazole-3-carboxylate

HRID 1774528Notes

Reaction equation

HRID 1774528 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:5]=2[CH3:14])[CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:18][C:19]1[C:24]([F:25])=[CH:23][C:22]([O:26][CH2:27][CH3:28])=[CH:21][C:20]=1[F:29].O>C1COCC1>[CH:1]1([C:4]2[N:8]([CH2:18][C:19]3[C:20]([F:29])=[CH:21][C:22]([O:26][CH2:27][CH3:28])=[CH:23][C:24]=3[F:25])[N:7]=[C:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:5]=2[CH3:14])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 467376162-(Bromomethyl)-5-ethoxy-1,3-difluorobenzeneHCID 89648788Ethyl 5-cyclopropyl-4-methyl-1H-pyrazole-3-carboxylate

Product 1

HCID 89649016ethyl 5-cyclopropyl-1-(4-ethoxy-2,6-difluorobenzyl)-4-methyl-1H-pyrazole-3-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

46.9 g of ethyl 5-cyclopropyl-4-methyl-1H-pyrazole-3-carboxylate 1-15-1 (266 mmol, 1.0 eq.) in 588 mL THF were cooled to 0° C. and 11.6 g sodiumhydride (60%, 290 mmol, 1.2 eq.) were added in small portions. The resulting suspension was diluted with 250 mL THF. 66.7 g 2-(bromomethyl)-5-ethoxy-1,3-difluorobenzene (266 mmol, 1.1 eq., commercially available) were added slowly. The reaction mixture was stirred at rt for 2 hours. 300 mL water was added and the THF was evaporated in vacuum. The aqueous residue was extracted with ethylacetate three times. The combined organic layers were dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to provide 79.8 g (195 mmol, 81%) of 89% pure target compound.

Workup

  1. customthe THF was evaporated in vacuum
  2. extractionThe aqueous residue was extracted with ethylacetate three times
  3. dry with materialThe combined organic layers were dried over a silicone
  4. filtrationfilter
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-a64f41c824ef4093a04d0fa24bb3bc0f
Source dataset
uspto-grants-2016_02
Patent number
US09260412B2

Reaction notes

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