Dimethylformamide → 5-chloro-3-ethyl-1-methyl-1h-pyrazole-4-carbaldehyde

HRID 2387141Notes

Reaction equation

HRID 2387141 reaction equation
O=P(Cl)(Cl)[Cl:3].C[N:7]([CH:9]=O)[CH3:8].[CH2:11]([C:13]1[CH:17]=[C:16]([OH:18])N(C)[N:14]=1)[CH3:12].C([O-])([O-])=O.[K+].[K+]>ClCCl>[Cl:3][C:9]1[N:7]([CH3:8])[N:14]=[C:13]([CH2:11][CH3:12])[C:17]=1[CH:16]=[O:18]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 178436950HCID 178436950, compound

Product 1

HCID 27575085-chloro-3-ethyl-1-methyl-1h-pyrazole-4-carbaldehydeYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

POCl3 (236.88 g, 1.543 mol, 144 mL) was added dropwise at 0° C. to DMF (59 g, 0.808 mol). The reaction mixture was then diluted with dichloromethane (200 mL), and: 3-ethyl-1-methyl-1H-pyrazol-5-ol (84.5 g, from Step 1) was added while stirring at 0° C. The mixture was refluxed for 3 h and then stirred overnight at room temperature. After this, ice-cold water (500 mL) was added rapidly at 0° C. to the reaction mixture in order to decompose the formylation agent. The organic layer was separated, and the aqueous phase extracted with chloroform several times. The organic layers were then washed with K2CO3 solution to obtain a weak alkaline media, dried over Na2SO4 and evaporated to give 51.2 g of an oily substance. The residual reaction mass was neutralized with K2CO3 to obtain a weak acidic media and extracted with chloroform. The combined extracts were concentrated and the residue purified by chromatography (dichloromethane) on a silica gel to give 71.3 g (62%) of the title product.

Workup

  1. temperatureThe mixture was refluxed for 3 h
  2. stirringstirred overnight at room temperature
  3. customThe organic layer was separated
  4. extractionthe aqueous phase extracted with chloroform several times
  5. washThe organic layers were then washed with K2CO3 solution
  6. customto obtain a weak alkaline media
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. customto give 51.2 g of an oily substance
  10. customto obtain a weak acidic media
  11. extractionextracted with chloroform
  12. concentrationThe combined extracts were concentrated
  13. customthe residue purified by chromatography (dichloromethane) on a silica gel

Sources & evidence

ORD record
ord-1c63f6e2cba2446887b74ec33742be1f
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

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