Acetyl chloride → 6-Bromo-7-fluoro-2,5-dimethyl-1,3-benzoxazole-4-carbonitrile

HRID 17357Notes

Reaction equation

HRID 17357 reaction equation
[NH2:1][C:2]1[C:9]([OH:10])=[C:8]([F:11])[C:7]([Br:12])=[C:6]([CH3:13])[C:3]=1[C:4]#[N:5].[C:14](Cl)(=O)[CH3:15].[Cl-].[NH4+]>C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>[Br:12][C:7]1[C:8]([F:11])=[C:9]2[O:10][C:14]([CH3:15])=[N:1][C:2]2=[C:3]([C:4]#[N:5])[C:6]=1[CH3:13]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 25517Ammonium ChlorideHCID 860975142-Amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile

Product 1

HCID 685843936-Bromo-7-fluoro-2,5-dimethyl-1,3-benzoxazole-4-carbonitrileYield 73%

Reagents, catalysts & solvents 2

HCID 81531DiisopropylethylamineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Diisopropylethylamine (22 ml, 0.126 mmol) was added to an ethyl acetate (400 ml) solution of 2-amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-75) (8.85 g, 36.1 mmol), cooled with ice, then acetyl chloride (3.85 ml, 54.2 mmol) was dropwise added, followed by stirring as such for 14 hours with gradually heating up to room temperature. With cooling with ice, aqueous saturated ammonium chloride solution was added, and the organic layer was collected. This was washed with saturated brine, dried over anhydrous sodium sulfate, then the solvent was evaporated away under reduced pressure. The resulting residue was suspended in toluene (500 ml), a catalytic amount of p-toluenesulfonic acid was added, followed by heating under reflux for 3 hours with a Dean-Stark device. After cooling, the solvent was evaporated away, the resulting residue was dissolved in ethyl acetate, washed with water. After drying over anhydrous sodium sulfate, the solvent was evaporated away under reduced pressure, the precipitated crystal was washed with isopropyl ether, then collected by filtration to obtain the entitled compound (7.07 g, 73%) as a colorless solid.

Workup

  1. temperaturecooled with ice
  2. additionwas added
  3. customthe organic layer was collected
  4. washThis was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated away under reduced pressure
  7. additiona catalytic amount of p-toluenesulfonic acid was added
  8. temperatureby heating
  9. temperatureunder reflux for 3 hours with a Dean-Stark device
  10. temperatureAfter cooling
  11. customthe solvent was evaporated away
  12. dissolutionthe resulting residue was dissolved in ethyl acetate
  13. washwashed with water
  14. dry with materialAfter drying over anhydrous sodium sulfate
  15. customthe solvent was evaporated away under reduced pressure
  16. washthe precipitated crystal was washed with isopropyl ether
  17. filtrationcollected by filtration

Sources & evidence

ORD record
ord-d5751a6de9ce4bea980568f8bdfecde6
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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