Formaldehyde → 3-Ethoxycarbonyl-5-difluoromethoxy-4-hydroxymethyl-1-methylpyrazole

HRID 1159492Notes

Reaction equation

HRID 1159492 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([OH:11])[N:8]([CH3:12])[N:7]=1)=[O:5])[CH3:2].[C:13](=[O:16])([O-])[O-].[K+].[K+].C=O.Cl[CH:22]([F:24])[F:23]>CN(C=O)C.O.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH2:13][OH:16])=[C:9]([O:11][CH:22]([F:24])[F:23])[N:8]([CH3:12])[N:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 6372ChlorodifluoromethaneHCID 11430Potassium Carbonate2×HCID 178469369HCID 178469369, compound

Product 1

HCID 667186593-Ethoxycarbonyl-5-difluoromethoxy-4-hydroxymethyl-1-methylpyrazoleYield 82%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 50 ml of DMF were suspended 8.5 g (0.05 mole) of the 3-ethoxycarbonyl-5-hydroxy-1-methylpyrazole synthesized in Reference Example 3 and 10.5 g (0.08 mole) of potassium carbonate. In this suspension being stirred at room temperature was placed 2.3 g (0.08 mole) of paraformaldehyde, followed by stirring at the same temperature for 1 hour. Then, 20.9 g (0.15 mole) of potassium carbonate was added. Therein was blown 8.6 g (0.10 mole) of chlorodifluoromethane. The reaction mixture was stirred at room temperature for 2 hours to give rise to a reaction. After the reaction, 200 ml of ethyl acetate and 200 ml of water were added. The organic layer, which appeared by phase separation, was separated. The aqueous layer was subjected to re-extraction with 50 ml of ethyl acetate three times. The organic layers were combined and washed with 50 ml of water, 30 ml of a saturated aqueous ammonium chloride solution and 30 ml of a saturated aqueous sodium chloride solution in this order. The resulting organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain 24.3 g (purity: 42.2%, yield: 82.0%) of a crude solution of title compound. The crude solution was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1) to obtain a title compound as white crystals.

Workup

  1. stirringby stirring at the same temperature for 1 hour
  2. stirringThe reaction mixture was stirred at room temperature for 2 hours
  3. customto give rise
  4. customto a reaction
  5. additionwere added
  6. customThe organic layer, which appeared by phase separation
  7. customwas separated
  8. extractionThe aqueous layer was subjected to re-extraction with 50 ml of ethyl acetate three times
  9. washwashed with 50 ml of water, 30 ml of a saturated aqueous ammonium chloride solution and 30 ml of a saturated aqueous sodium chloride solution in this order
  10. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-892c125766b040c784cc0094fdcf2ef7
Source dataset
uspto-grants-2010_10
Patent number
US07812175B2

Reaction notes

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