Reaction #9433

Reaction equation

5′-bromospiro{cyclohexane-1,3′-[3H]indol}-2′(1′H)-one 2′(O-benzyloxime)

sodium carbonate

3-fluoro-5-cyano-bromobenzene

potassium acetate

→

desired product

Yield 66.0%

3-[1′,2′-DIHYDRO-2′-(HYDROXYIMINO)SPIRO[CYCLOHEXANE-1,3′-[3H]INDOL]-5′YL]-5-FLUOROBENZONITRILE

Yield 66.0%

Solvents

DMF

Conditions

Workup

1. 1
   Temperatureheating at 80° C.
2. 2
   Temperaturethe reaction was cooled
3. 3
   Otherpartitioned between water and ethyl acetate
4. 4
   Washthe organic layer was washed with brine
5. 5
   Dryingdried (MgSO4)
6. 6
   Otherevaporated
7. 7
   OtherThe residue was purified by column chromatography (SiO2, EtOAc:hexane 1:20)

Procedure

To a solution of 3-fluoro-5-cyano-bromobenzene (0.4 g, 2.0 mmol) in dry DMF (10 ml) was added diboron pinacolate ester (0.63 g, 2.5 mmol), potassium acetate (0.65 g, 6.7 mmol) and PdCl2 (dppf) (0.2 g) and the reaction was heated to 80° C. under a nitrogen atmosphere. After 8 h. from 5′-bromospiro{cyclohexane-1,3′-[3H]indol}-2′(1′H)-one 2′(O-benzyloxime) (0.2 g, 0.5 mmol), PdCl2 (dppf) (0.05 g) and sodium carbonate (1.30 g, 12.5 mmol) were added and heating at 80° C. was continued. After 8 h., the reaction was cooled and partitioned between water and ethyl acetate, the organic layer was washed with brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography (SiO2, EtOAc:hexane 1:20) to give the desired product (0.14 g, 0.33 mmol, 66%).

Source