Acetic Anhydride → HCID 22933528, compound

HRID 1269846Notes

Reaction equation

HRID 1269846 reaction equation
[C:1]([O:4]C(=O)C)(=O)[CH3:2].[CH3:8][O:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[C:12]([CH3:17])[C:11]=1[C:18]([F:21])([F:20])[F:19].C([O-])(=O)C.[K+].[N:27](OCCC(C)C)=O>C(OCC)(=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([N:14]1[C:13]2[C:12](=[C:11]([C:18]([F:20])([F:19])[F:21])[C:10]([O:9][CH3:8])=[CH:16][CH:15]=2)[CH:17]=[N:27]1)(=[O:4])[CH3:2]

Participants

7

Reactant 4

HCID 7918Acetic Anhydride2×HCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 22933386HCID 22933386, compound

Product 1

HCID 22933528HCID 22933528, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
65 °C

Procedure

Acetic anhydride (377 μl, 4.00 mmol) was added dropwise to a solution of 4-methoxy-2-methyl-3-(trifluoromethyl)aniline (513 mg, 2.50 mmol) in ethyl acetate (3.0 ml) at room temperature. Ethyl acetate (4.5 ml) was added to the solidified reaction solution and the resulting mixture was slowly heated to 65° C. and stirred for 15 minutes while maintaining the temperature. The resulting reaction solution was cooled to room temperature, followed by adding thereto acetic anhydride (708 μl, 7.50 mmol), tetrabutylammonium bromide (40.3 mg, 0.125 mmol), potassium acetate (491 mg, 5.00 mmol) and isopentyl nitrite (437 μl, 3.25 mmol) in that order at room temperature. The resulting mixture was slowly heated to 65° C. and stirred for 6 hours while maintaining the temperature. After cooling, the mixture was partitioned and extracted with water and ethyl acetate, and the organic layer was washed with a 5% aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure to obtain a crude product (800 mg). The crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 to 6/1) to obtain 1-acetyl-5-methoxy-4-(trifluoromethyl)-1H-indazole (496 mg, 77%).

Workup

  1. temperaturewhile maintaining the temperature
  2. customThe resulting reaction solution
  3. temperaturewas cooled to room temperature
  4. additionby adding
  5. customat room temperature
  6. temperatureThe resulting mixture was slowly heated to 65° C.
  7. stirringstirred for 6 hours
  8. temperaturewhile maintaining the temperature
  9. temperatureAfter cooling
  10. customthe mixture was partitioned
  11. extractionextracted with water and ethyl acetate
  12. washthe organic layer was washed with a 5% aqueous sodium chloride solution
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated under reduced pressure
  16. customto obtain a crude product (800 mg)
  17. customThe crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 to 6/1)

Sources & evidence

ORD record
ord-058db738499f497ba53da0d55e27c70f
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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