Lithium Hexamethyldisilazide → (3E)-3-(4-bromo-5,5-dimethylfuran-2(5H)-ylidene)-5,6-difluoro-1,3-dihydro-2H-indol-2-one
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6](=[O:12])[CH2:5]2.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:23][C:24]1[C:28]([CH3:30])([CH3:29])[O:27][C:26](=O)[CH:25]=1>C1COCC1>[Br:23][C:24]1[C:28]([CH3:30])([CH3:29])[O:27]/[C:26](=[C:5]2/[C:6](=[O:12])[NH:7][C:8]3[C:4]/2=[CH:3][C:2]([F:1])=[C:10]([F:11])[CH:9]=3)/[CH:25]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 5, 6-difluorooxindole (450 mg, 2.66 mmol) in THF (20 mL) at 0° C., was added 1 M LiHMDS in THF (5.3 mL, 5.3 mmol). The reaction mixture was stirred at 0° C. for 10 minutes. 4-bromo-5, 5-dimethyl-5H-furan-2-one (340 mg, 1.78 mmol) was then added. The reaction mixture was stirred at 0° C. for 30 min., and then at room temperature for an additional 30 min and quenched with 2.5M aqueous H2SO4 (3 mL). The resulting mixture was stirred at room temperature for 16 hours and poured into water (100 mL). The precipitates were filtered, washed with water and dried in vacuo to yield (3E)-3-(4-bromo-5,5-dimethylfuran-2(5H)-ylidene)-5,6-difluoro-1,3-dihydro-2H-indol-2-one as yellow solid. Yield: 547 mg, 90%.
Workup
- stirringThe reaction mixture was stirred at 0° C. for 30 min.
- waitat room temperature for an additional 30 min
- customquenched with 2.5M aqueous H2SO4 (3 mL)
- stirringThe resulting mixture was stirred at room temperature for 16 hours
- additionpoured into water (100 mL)
- filtrationThe precipitates were filtered
- washwashed with water
- customdried in vacuo
Sources & evidence
- ORD record
- ord-46e2cd66b1f544aa95854604b132a2b4
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08367664B2
Reaction notes
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