Reacción #3118

Ecuación de reacción

1-Acetyl-6-bromo-5-hydroxyindoline

methyl 2-chloro-2,2-difluoroacetate

methyl 2-chloro-2,2-difluoroacetate

potassium carbonate

potassium carbonate

→

title compound

1-Acetyl-6-bromo-5-difluoromethoxyindoline

Disolventes

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroplaced in a 65° C.
2. 2
   Temperaturaheated for 18 hr
3. 3
   OtroThe solvent was then removed in vacuo
4. 4
   Otrothe residue was partitioned between cold 3N HCl and ether
5. 5
   ExtracciónThe aqueous layer was extracted three times with ether
6. 6
   Lavadothe combined organic extracts were washed with brine
7. 7
   Secadodried (Na2SO4)
8. 8
   Filtraciónfiltered
9. 9
   Otroevaporated
10. 10
    OtroThe solid was purified by flash chromatography (2% MeOH/CH2Cl2)

Procedimiento

1-Acetyl-6-bromo-5-hydroxyindoline (2 g, 7.8 mmol), methyl 2-chloro-2,2-difluoroacetate (0.82 ml, 7.8 mmol) and potassium carbonate (1.08 g, 7.8 mmol) were suspended in N,N-dimethylformamide (20 mL) under an argon atmosphere and placed in a 65° C. oil bath. After 3 hr, additional methyl 2-chloro-2,2-difluoroacetate (0.3 ml, 2.8 mmol) and potassium carbonate (0.3 g, 2.2 mmol) was added and heated for 18 hr. The solvent was then removed in vacuo and the residue was partitioned between cold 3N HCl and ether. The aqueous layer was extracted three times with ether, the combined organic extracts were washed with brine, dried (Na2SO4), filtered and evaporated. The solid was purified by flash chromatography (2% MeOH/CH2Cl2) to provide the title compound as a white solid

Fuente