Reaction #8908

Reaction equation

N-methylmorpholine-N-oxide

product

1-[6-(2-Chlorophenyl)-5-(4-chlorophenyl)-3-methylfuro[2,3-b]pyridin-2-yl]-2,2-dimethylpropan-1-one

N-bromosuccinimide

2,2′-azobisisobutyronitrile

→

title compound

6-(2-Chlorophenyl)-5-(4-chlorophenyl)-2-(2,2-dimethylpropanoyl)furo[2,3-b]pyridine-3-carbaldehyde

Solvents

CCl4

Conditions

Workup

1. 1
   OtherA 10 mL rb flask equipped with a magnetic stir bar
2. 2
   TemperatureThe reaction mixture was heated
3. 3
   Temperatureto reflux under a nitrogen atmosphere for 2 h
4. 4
   Filtrationfiltered
5. 5
   OtherThe filtrate was evaporated in vacuo
6. 6
   workup.DISSOLUTIONthe residue was then redissolved in 2 mL of DMSO
7. 7
   workup.ADDITIONThe solution containing the crude bromination product
8. 8
   workup.ADDITIONwas added
9. 9
   OtherThe reaction vessel was sealed
10. 10
    Temperatureheated at 150° C. for 2–3 min
11. 11
    TemperatureAfter the reaction mixture had cooled to room temperature
12. 12
    Otherit was partitioned between EtOAc and 10% aq. NaHSO4
13. 13
    Extractionextracted
14. 14
    WashThe organic layer was washed with 10% aq. NaHSO4, water, brine
15. 15
    Dryingdried (MgSO4)
16. 16
    Filtrationfiltered
17. 17
    Otherevaporated
18. 18
    OtherThe residue was purified on a silica gel flash chromatography column
19. 19
    Washeluted with 0–10% EtOAc-hexane
20. 20
    OtherEvaporation of the purified fractions
21. 21
    Otherdrying in vacuo

Procedure

A 10 mL rb flask equipped with a magnetic stir bar was charged with 0.227 g (0.52 mmol) of the product of Example 89, 0.101 g (0.57 mmol) of N-bromosuccinimide, 3 mL CCl4 and ca. 5 mg of 2,2′-azobisisobutyronitrile (AIBN). The reaction mixture was heated to reflux under a nitrogen atmosphere for 2 h then cooled to room temperature and filtered. The filtrate was evaporated in vacuo, and the residue was then redissolved in 2 mL of DMSO. The solution containing the crude bromination product was transferred to a 10 mL reaction tube of a CEM Corporation Discover 300 Watt microwave reactor and 73 mg (0.62 mmol) of N-methylmorpholine-N-oxide was added. The reaction vessel was sealed, placed in the microwave reactor and heated at 150° C. for 2–3 min. After the reaction mixture had cooled to room temperature, it was partitioned between EtOAc and 10% aq. NaHSO4 and extracted. The organic layer was washed with 10% aq. NaHSO4, water, brine, dried (MgSO4), filtered and evaporated. The residue was purified on a silica gel flash chromatography column eluted with 0–10% EtOAc-hexane. Evaporation of the purified fractions and drying in vacuo afforded the title compound. HPLC/MS: 452.1 (M+1), 454.0 (M+3); Rt=4.63 min.

Source