Dimethylformamide → 1-(2,2-Dimethyl-propyl)-1H-pyrazole-4-carbaldehyde

HRID 420327Notes

Reaction equation

HRID 420327 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]([CH3:15])([CH3:14])[CH2:8][N:9]1[CH:13]=[CH:12][CH:11]=[N:10]1.CN([CH:19]=[O:20])C>>[CH3:6][C:7]([CH3:15])([CH3:14])[CH2:8][N:9]1[CH:13]=[C:12]([CH:19]=[O:20])[CH:11]=[N:10]1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 230883491-(2,2-dimethyl-propyl)-1H-pyrazole

Product 1

HCID 866395471-(2,2-Dimethyl-propyl)-1H-pyrazole-4-carbaldehyde

Conditions

Temperature
0 °C

Procedure

A flask charged with anhydrous DMF (400 mL) was cooled to 0° C., to which phosphorous oxychloride (114 g, 0.74 mol) was added dropwise, and the temperature was kept below 10° C. The stirring was continued for 1 h and it was allowed to rise to room temperature. Then it was cooled to 0° C. again, and a solution of 1-(2,2-dimethyl-propyl)-1H-pyrazole (51.1 g, 0.37 mol, CAS registry 725746-83-8) in DMF (100 mL) was added dropwise. Then it was heated to 100° C. overnight. After cooling, the reaction was quenched by slow addition of cold water, and it was neutralized with aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The resulting residue was purified by column chromatograph on silicagel (petroleum ether-EtOAc 10:1) to give the title compound as light yellow oil: ESIMS [M+H]+=167; 1H NMR (400 MHz, DMSO-d6): δ 9.80 (s, 1H), 8.42 (s, 1H), 7.98 (s, 1H), 3.99 (s, 2H), 0.90 (s, 9H).

Workup

  1. additionwas added dropwise
  2. customwas kept below 10° C
  3. customto rise to room temperature
  4. temperatureThen it was heated to 100° C. overnight
  5. temperatureAfter cooling
  6. customthe reaction was quenched by slow addition of cold water, and it
  7. extractionextracted with EtOAc
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe resulting residue was purified by column chromatograph on silicagel (petroleum ether-EtOAc 10:1)

Sources & evidence

ORD record
ord-a47b7d45672b4774877122a22700647e
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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