Ethyl 2-(ethoxymethylene)-4,4,4-trifluoroacetoacetate → ethyl 1-(4-cyanophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1160565Notes

Reaction equation

HRID 1160565 reaction equation
C(O/[CH:4]=[C:5](/[C:11](=O)[C:12]([F:15])([F:14])[F:13])\[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.Cl.[NH:18]([C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1)[NH2:19]>C(O)C>[C:24]([C:23]1[CH:26]=[CH:27][C:20]([N:18]2[C:11]([C:12]([F:13])([F:14])[F:15])=[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:4]=[N:19]2)=[CH:21][CH:22]=1)#[N:25]

Participants

4

Reactant 2

HCID 2737179Ethyl 2-(ethoxymethylene)-4,4,4-trifluoroacetoacetateHCID 162129624-Cyanophenylhydrazine Hydrochloride

Product 1

HCID 59516077ethyl 1-(4-cyanophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylateYield 77.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
-10 °C

Procedure

A solution of (Z)-ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate (2.41 g, 10.03 mmol) in ethanol (10 mL) was added dropwise to a stirred solution of 4-hydrazinylbenzonitrile hydrochloride (1.702 g, 10.03 mmol), in ethanol (50 mL) cooled to −10° C. The resulting solution was allowed to stir at room temperature for 16 hours. The reaction mixture was evaporated to dryness and the residue redissolved in EtOAc (100 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica (120 g) chromatography, elution gradient 10 to 60% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford ethyl 1-(4-cyanophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2.400 g, 77%) as a white solid.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionthe residue redissolved in EtOAc (100 mL)
  3. washwashed sequentially with water (50 mL) and saturated brine (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica (120 g) chromatography, elution gradient 10 to 60% EtOAc in isohexane
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-d9bdb4793101484c9f9c332e69ed2d0d
Source dataset
uspto-grants-2010_10
Patent number
US07816391B2

Reaction notes

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