Hydrochloric Acid → 2,4-dichloro-3-(1-methyl-3-methylcarbonyl-1H-pyrazol-5-yl)benzoic acid

HRID 1276126Notes

Reaction equation

HRID 1276126 reaction equation
[Cl:1][C:2]1[C:10]([C:11]2[CH:15]=[C:14]([C:16]([CH3:18])=[O:17])[NH:13][N:12]=2)=[C:9]([Cl:19])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[H-].[Na+].[CH3:22]I.[Cl-].[Na+].Cl>O1CCCC1>[Cl:1][C:2]1[C:10]([C:11]2[N:12]([CH3:22])[N:13]=[C:14]([C:16]([CH3:18])=[O:17])[CH:15]=2)=[C:9]([Cl:19])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 6328Methyl iodide3×HCID 24758Sodium hydride2×HCID 221149482,4-dichloro-3-(5-methylcarbonyl-1H-pyrazol-3-yl)benzoic acid

Product 1

HCID 221149072,4-dichloro-3-(1-methyl-3-methylcarbonyl-1H-pyrazol-5-yl)benzoic acidYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

At room temperature and under protective gas, 2.0 g (6.7 mmol) of 2,4-dichloro-3-(5-methylcarbonyl-1H-pyrazol-3-yl)benzoic acid in 50 ml of tetrahydrofuran were added dropwise to 0.40 g (16.7 mmol) of sodium hydride. The mixture was stirred for 1 hour, 4.8 g (33.4 mmol) of methyl iodide were added, the mixture was stirred for 10 hours and another 4.8 g (33.4 mmol) of methyl iodide were added, the mixture was stirred at 50° C. for 5 hours and 0.16 g (6.7 mmol) of sodium hydride and another 4.8 g (33.4 mmol) of methyl iodide were then added and the mixture was heated at 50° C. for 1 hour. After cooling, the reaction mixture was stirred into 100 ml of a sodium chloride solution and a pH of 1 was adjusted using hydrochloric acid. The product was then extracted with methyl tert-butyl ether and the combined organic phases were washed with water, dried and concentrated. The residue was then chromatographed over silica gel (eluent: toluene/tetrahydrofuran/acetic acid=8/1/1). 1.25 g (60% of theory) of 2,4-dichloro-3-(1-methyl-3-methylcarbonyl-1H-pyrazol-5-yl)benzoic acid were obtained.

Workup

  1. stirringthe mixture was stirred for 10 hours
  2. stirringthe mixture was stirred at 50° C. for 5 hours
  3. temperatureAfter cooling
  4. extractionThe product was then extracted with methyl tert-butyl ether
  5. washthe combined organic phases were washed with water
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was then chromatographed over silica gel (eluent: toluene/tetrahydrofuran/acetic acid=8/1/1)

Sources & evidence

ORD record
ord-29c5cd1ebdc14aa29cd0b89d00d4ea19
Source dataset
uspto-grants-2000_12
Patent number
US06165944

Reaction notes

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