Dimethylformamide → 1-Ethyl-N-methoxy-N,5-dimethyl-1H-pyrazole-3-carboxamide

HRID 1825347Notes

Reaction equation

HRID 1825347 reaction equation
[CH2:1]([N:3]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([OH:11])=O)=[N:4]1)[CH3:2].C[N:13]([CH3:16])C=O.C(Cl)(=O)[C:18](Cl)=[O:19]>ClCCl>[CH3:18][O:19][N:13]([CH3:16])[C:9]([C:5]1[CH:6]=[C:7]([CH3:8])[N:3]([CH2:1][CH3:2])[N:4]=1)=[O:11]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 163948271-Ethyl-5-methyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 221453881-Ethyl-N-methoxy-N,5-dimethyl-1H-pyrazole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-Ethyl-5-methylpyrazole-3-carboxylic acid (5.25 g) in dry dichloromethane (100 ml) containing N,N-dimethylformamide (0.26 ml) was cooled in an ice-bath and treated with a solution of oxalyl chloride (3.27 ml) in dichloromethane (25 ml), added dropwise. The mixture was stirred in the cold for 25 min, and then allowed to warm to room temperature, when evolution of a gas was observed. After 10 min the solvent was removed by evaporation in vacuo and toluene was added and removed (×2) to ensure any residual HCl and oxalyl chloride had been removed. The resultant acid chloride was redissolved in dry dichloromethane and then treated with N,O-dimethylhydroxylamine hydrochloride (3.61 g). The mixture was cooled in an ice-bath and treated with pyridine (6.0 ml). The mixture was then allowed to stir at room temperature for 1.5 h and then diluted with ether (100 ml) and washed with brine. The organic layer was then dried (MgSO4) and evaporated to leave an oil. This was the chromatographed on silica gel, loading in dichloromethane, and eluting, with ethyl acetate/hexane mixtures to give, after evaporation of requisite fractions, the hydroxamate (5.2 g) as a solid; υmax(CH2Cl2) 2982, 2937, 1641, 1489, 1445, 1379,and 975 cm−1; δ(CDCl3) 1.43 (3H, t, J 7.3 Hz), 2.29 (3H, s), 3.42 (3H, s), 3.76 (3H, s, ), 4.13 (2H, q, J 7.3 Hz), 6.49 (1H, s); (Found m/z 197.1164. C9H15N3O2 requires m/z 197.1164).

Workup

  1. temperaturewas cooled in an ice-bath
  2. additionadded dropwise
  3. customAfter 10 min the solvent was removed by evaporation in vacuo and toluene
  4. additionwas added
  5. customremoved (×2)
  6. customhad been removed
  7. dissolutionThe resultant acid chloride was redissolved in dry dichloromethane
  8. additiontreated with N,O-dimethylhydroxylamine hydrochloride (3.61 g)
  9. temperatureThe mixture was cooled in an ice-bath
  10. additiontreated with pyridine (6.0 ml)
  11. stirringto stir at room temperature for 1.5 h
  12. additiondiluted with ether (100 ml)
  13. washwashed with brine
  14. dry with materialThe organic layer was then dried (MgSO4)
  15. customevaporated
  16. customto leave an oil
  17. customchromatographed on silica gel, loading in dichloromethane
  18. washeluting, with ethyl acetate/hexane
  19. customto give
  20. customafter evaporation of requisite fractions

Sources & evidence

ORD record
ord-10c3b123393d4207b94e1910d293c72a
Source dataset
uspto-grants-2006_05
Patent number
US07045619B2

Reaction notes

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