Ethyl chloroformate → HCID 19791291, compound

HRID 1655245Notes

Reaction equation

HRID 1655245 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][N:11]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)=[O:14])[N:10]=[C:9]2[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[N:6][CH:7]=1.Cl[C:35]([O:37][CH2:38][CH3:39])=[O:36]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][N:11]([C:13]([N:15]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:16]3[CH:17]=[CH:18][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:20][CH:21]=3)=[O:14])[N:10]=[C:9]2[C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)=[N:6][CH:7]=1

Participants

3

Reactant 2

HCID 10928Ethyl chloroformateHCID 19791323HCID 19791323, compound

Product 1

HCID 19791291HCID 19791291, compoundYield 60%

Procedure

Sodium hydride (240 mg, 6.00 mmol as a 60 percent slurry in mineral oil) was extracted 3 times with 2 mL portions of dry hexane under an inert atmosphere and then 15 mL of tetrahydrofuran was added and the mixture cooled by stirring in an ice bath. 4-(5-Chloro-2-pyridinyl)-4,5-dihydro-3-(4-fluorophenyl)-N-(4-trifluoromethoxyphenyl)-1H-pyrazole-1-carboxamide (958 mg, 2.00 mmol) was then added in one portion and the mixture allowed to react for 30 min. Ethyl chloro-formate (0.573 mL, 6.00 mmol) was then added with cooling and stirring and the mixture allowed to react at 0°-10° C. for 30 min. The resulting mixture was partitioned between saturated aqueous ammonium chloride and ether. The ethereal phase was dried over magnesium sulfate, and then concentrated by evaporation under reduced pressure. The residue was triturated with 20 mL of ether, refrigerated for about 1 hr, and then recovered by filtration. It was then recrystallized from a mixture of hexane and acetone to obtain 660 mg of the title compound as white crystals melting at 159.5°-161° C. (60 percent yield)

Workup

  1. extractionSodium hydride (240 mg, 6.00 mmol as a 60 percent slurry in mineral oil) was extracted 3 times with 2 mL portions of dry hexane under an inert atmosphere
  2. addition15 mL of tetrahydrofuran was added
  3. temperaturethe mixture cooled
  4. customto react for 30 min
  5. temperaturewith cooling
  6. stirringstirring
  7. customto react at 0°-10° C. for 30 min
  8. customThe resulting mixture was partitioned between saturated aqueous ammonium chloride and ether
  9. dry with materialThe ethereal phase was dried over magnesium sulfate
  10. concentrationconcentrated by evaporation under reduced pressure
  11. customThe residue was triturated with 20 mL of ether
  12. filtrationrecovered by filtration
  13. customIt was then recrystallized from a mixture of hexane and acetone

Sources & evidence

ORD record
ord-74bc9abb66fb4916bedabd7f22c81ad3
Source dataset
uspto-grants-1993_10
Patent number
US05250532

Reaction notes

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