Reaktion #45835

Reaktionsgleichung

1-hydroxybenzotriazole

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

triethylamine

4-amino-6-fluoro-5-hydroxy-2-methylbiphenyl-3-carbonitrile

2-furylacetic acid

→

compound

Ausbeute 57.0%

7-Fluoro-2-(2-furylmethyl)-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Ausbeute 57.0%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction liquid
2. 2
   Einengenwas concentrated under reduced pressure
3. 3
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
4. 4
   Waschenwashed with water and saturated brine
5. 5
   TrocknenThe organic layer was dried over anhydrous sodium sulfate
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   workup.DISSOLUTIONthe resulting residue was dissolved in xylene (20 ml)
8. 8
   workup.ADDITIONpyridinium p-toluenesulfonate (50 mg) was added
9. 9
   Temperaturby heating
10. 10
    Temperaturunder reflux in an oil bath at 160° C. for 1 hour
11. 11
    SonstigeThe reaction liquid
12. 12
    Einengenwas concentrated under reduced pressure
13. 13
    workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
14. 14
    Waschenwashed with saturated brine
15. 15
    TrocknenAfter drying over anhydrous sodium sulfate
16. 16
    Sonstigethe insoluble matter was separated by filtration
17. 17
    Sonstigethe residue obtained by concentration under reduced pressure
18. 18
    Sonstigewas purified by silica gel column chromatography (eluent, n-hexane

Vorschrift

With cooling with ice, 1-hydroxybenzotriazole (134 mg, 0.991 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (174 mg, 0.908 mmol) and triethylamine (127 μl, 0.980 mmol) were added to an acetonitrile (8 ml) solution of 4-amino-6-fluoro-5-hydroxy-2-methylbiphenyl-3-carbonitrile (I-41) (200 mg, 0.826 mmol) and 2-furylacetic acid (115 mg, 0.908 mmol), followed by stirring at room temperature for 16 hours. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, and washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate, then concentrated under reduced pressure, and the resulting residue was dissolved in xylene (20 ml), then pyridinium p-toluenesulfonate (50 mg) was added, followed by heating under reflux in an oil bath at 160° C. for 1 hour. The reaction liquid was concentrated under reduced pressure, then the residue was dissolved in ethyl acetate, washed with saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, and the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=4:1, v/v) to obtain the entitled compound (155 mg, 57%) as a pale yellow solid.

Quelle