Reaktion #45635

Reaktionsgleichung

2-amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile

acetyl chloride

ammonium chloride

→

compound

Ausbeute 73.0%

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

Ausbeute 73.0%

Lösungsmittel

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled with ice
2. 2
   workup.ADDITIONwas added
3. 3
   Sonstigethe organic layer was collected
4. 4
   WaschenThis was washed with saturated brine
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   Sonstigethe solvent was evaporated away under reduced pressure
7. 7
   workup.ADDITIONa catalytic amount of p-toluenesulfonic acid was added
8. 8
   Temperaturby heating
9. 9
   Temperaturunder reflux for 3 hours with a Dean-Stark device
10. 10
    TemperaturAfter cooling
11. 11
    Sonstigethe solvent was evaporated away
12. 12
    workup.DISSOLUTIONthe resulting residue was dissolved in ethyl acetate
13. 13
    Waschenwashed with water
14. 14
    TrocknenAfter drying over anhydrous sodium sulfate
15. 15
    Sonstigethe solvent was evaporated away under reduced pressure
16. 16
    Waschenthe precipitated crystal was washed with isopropyl ether
17. 17
    Filtrationcollected by filtration

Vorschrift

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.

Quelle