Hydrochloric Acid → 5-chloro-1-cyclohexyl-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 12879

Reaction equation

HRID 12879 reaction equation
N(OC(C)(C)C)=O.[CH2:8]([O:10][C:11]([C:13]1[CH:14]=[N:15][N:16]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:17]=1N)=[O:12])[CH3:9].[ClH:25]>C(#N)C.[Cu]Cl>[CH2:8]([O:10][C:11]([C:13]1[CH:14]=[N:15][N:16]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:17]=1[Cl:25])=[O:12])[CH3:9]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 351028ethyl 5-amino-1-cyclohexyl-1H-pyrazole-4-carboxylate

Product 1

HCID 670209265-chloro-1-cyclohexyl-1H-pyrazole-4-carboxylic acid ethyl esterYield 42%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6342AcetonitrileSolvent2×

Procedure

Copper(I) chloride (2.500 g, 25.25 mmol) was suspended in 7.0 mL cold (ice/acetone bath) anhydrous acetonitrile. t-Butyl nitrite (5.75 mL, 90%, 43.56 mmol) was added, followed by a suspension of 5-amino-1-cyclohexyl-1H-pyrazole-4-carboxylic acid ethyl ester (4.408 g, 18.58 mmol) in 27.0 mL acetonitrile. The mixture was stirred at room temperature for 45 minutes and then at 70° C. for 1.25 hour. The mixture was cooled to room temperature, slowly added to 6N HCl (17.5 mL) and then extracted with methylene chloride. The organic phase was washed sequentially with water and brine. The aqueous phases were back extracted with a second portion of methylene chloride. The two organic phases were combined, dried over sodium sulfate and concentrated in vacuo. The crude residue was chromatographed by flash chromatography eluting with a gradient of 10-50% ethyl acetate/hexanes to give 5-chloro-1-cyclohexyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.98 g; 42%). Mass spectrum: m/z: 257.3 (M+H).

Workup

  1. waitat 70° C. for 1.25 hour
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted with methylene chloride
  4. washThe organic phase was washed sequentially with water and brine
  5. extractionThe aqueous phases were back extracted with a second portion of methylene chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was chromatographed by flash chromatography
  9. washeluting with a gradient of 10-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b3919ed3436a4960839e99ad25df6759
Source dataset
uspto-grants-2010_06
Patent number
US07728029B2

Linked notes

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