Sodium hydride → 1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carbaldehyde

HRID 220485Notes

Reaction equation

HRID 220485 reaction equation
[NH:1]1[CH:5]=[C:4]([CH:6]=[O:7])[CH:3]=[N:2]1.[H-].[Na+].[F:10][C:11]([F:25])([F:24])[CH2:12]OS(C1C=CC(C)=CC=1)(=O)=O>CN(C=O)C>[F:10][C:11]([F:25])([F:24])[CH2:12][N:1]1[CH:5]=[C:4]([CH:6]=[O:7])[CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67942Ethanol, 2,2,2-trifluoro-, 1-(4-methylbenzenesulfonate)HCID 51306731H-pyrazole-4-carbaldehyde

Product 1

HCID 196195521-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

Add 1H-pyrazole-4-carbaldehyde (0.400 g, 4.16 mmol) as a solution in DMF (2 mL) dropwise to a suspension of sodium hydride (0.333 g, 8.32 mmol) in DMF (5 mL) at 0° C. Stir for 15 min. at 0° C. Add 2,2,2-trifluoroethyl-p-toluenesulfonate (1.27 g, 5.00 mmol) and DMF (3 mL) to the reaction mixture. Heat to 60° C. for 18 hr. Quench with aqueous saturated sodium bicarbonate solution and add ethyl acetate. Separate organic layer. Extract aqueous layer twice with ethyl acetate, wash combined organics with brine, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 100:0 ethyl acetate:hexanes) to give the title preparation (309 mg, 42%). GC-MS: m/z=178 [M+].

Workup

  1. temperatureHeat to 60° C. for 18 hr
  2. customQuench with aqueous saturated sodium bicarbonate solution
  3. additionadd ethyl acetate
  4. washExtract aqueous layer twice with ethyl acetate, wash
  5. dry with materialdry (magnesium sulfate)
  6. filtrationfilter
  7. concentrationconcentrate
  8. custompurify
  9. wash(silica gel chromatography, eluting with 0:100 to 100:0 ethyl acetate:hexanes)
  10. customto give the title
  11. custompreparation (309 mg, 42%)

Sources & evidence

ORD record
ord-20a3258226dc44fda1b718e3a563a5b0
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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