Hydrochloric Acid → Ethyl 5-Chloro-1-methyl-1H-pyrazole-4-carboxylate

HRID 2351237Notes

Reaction equation

HRID 2351237 reaction equation
N[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].N([O-])=O.[Na+].[ClH:17]>C(O)(=O)C.P(=O)(O)(O)O.O>[Cl:17][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

7

Reactant 3

HCID 313Hydrochloric Acid2×HCID 271299Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 2758821Ethyl 5-Chloro-1-methyl-1H-pyrazole-4-carboxylateYield 44.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1004Phosphoric AcidSolvent

Procedure

23.7 g of ethyl 5-amino-1-methylpyrazole-4-carboxylate is dissolved in a mixture of 50 ml of concentrated hydrochloric acid, 34 ml of acetic acid and 28 ml of phosphoric acid. A solution of 10 g of sodium nitrite in 25 ml of water is added dropwise to the solution while cooling at -4° C. to -6° C. and stirring over a period of 35 minutes to prepare the diazonium salt solution. While cooling at 3° C. to 4° C., the diazonium salt solution is added dropwise to 140 ml of concentrated hydrochloric acid containing 13.9 g of cuprous chloride over a period of 45 minutes. The mixture is stirred at the same temperature for 1 hour, poured into 2l of ice water, and extracted with ethyl acetate. The extract is washed with a saturated aqueous sodium chloride solution, a saturated aqueous sodium bicarbonate solution and a saturated sodium chloride solution in that order, and dried over anhydrous sodium sulfate. Ethyl acetate is evaporated under reduced pressure, and the residue is purified by silica gel column chromatography (eluent, ethyl acetate:toluene=1:1) to give 11.7 g of the titled compound. Yield 44.3%.

Workup

  1. temperaturewhile cooling at -4° C. to -6° C.
  2. temperatureWhile cooling at 3° C. to 4° C.
  3. stirringThe mixture is stirred at the same temperature for 1 hour
  4. extractionextracted with ethyl acetate
  5. washThe extract is washed with a saturated aqueous sodium chloride solution
  6. dry with materiala saturated aqueous sodium bicarbonate solution and a saturated sodium chloride solution in that order, and dried over anhydrous sodium sulfate
  7. customEthyl acetate is evaporated under reduced pressure
  8. customthe residue is purified by silica gel column chromatography (eluent, ethyl acetate:toluene=1:1)

Sources & evidence

ORD record
ord-18f4a5bf887d40e48316b982fba6870d
Source dataset
uspto-grants-1989_10
Patent number
US04872901

Reaction notes

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