tert-Butyl acrylate → (E)-tert-Butyl 3-(1H-pyrrolo[2,3-b]pyridin-5-yl)acrylate t-butyl acrylate
Reaction equation
[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])(=[O:4])[CH:2]=[CH2:3].C(N(C(C)C)CC)(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:42]1[CH:43]=[C:44]2[CH:50]=[CH:49][NH:48][C:45]2=[N:46][CH:47]=1>C(#N)CC.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:6]([O:5][C:1](=[O:4])[CH:2]=[CH2:3])([CH3:9])([CH3:8])[CH3:7].[NH:48]1[C:45]2=[N:46][CH:47]=[C:42](/[CH:3]=[CH:2]/[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[CH:43]=[C:44]2[CH:50]=[CH:49]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
tert-Butyl acrylate (5.9 mL, 40.6 mmol), diisopropylethylamine (3.5 mL, 20.3 mmol) and P(o-tolyl)3 (618 mg, 2.0 mmol) were successively added to a suspension of 5-bromo-1H-pyrrolo[2,3-b]pyridine (2.0 g, 10.15 mmol) in propionitrile (40 mL) and dimethylformamide (10 mL). The resulting mixture was purged with argon prior to the addition of palladium acetate (227 mg, 1.0 mmol). The mixture was then purged with argon a second time and refluxed overnight. The reaction mixture was filtered on Celite®. The filtrate was concentrated to dryness and the residue was solubilized in ethyl acetate (3×100 mL). The organic layers were washed with a saturated solution of sodium chloride (3×50 mL), dried over sodium sulfate, filtered and concentrated to dryness. The crude was purified by flash chromatography on silica gel using dichloromethane/ethyl acetate (1:0 to 7:3) as eluent. The title compound was obtained as a yellow solid (465 mg, 28%)
Workup
- customThe resulting mixture was purged with argon
- customThe mixture was then purged with argon a second time
- temperaturerefluxed overnight
- filtrationThe reaction mixture was filtered on Celite®
- concentrationThe filtrate was concentrated to dryness
- washThe organic layers were washed with a saturated solution of sodium chloride (3×50 mL)
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated to dryness
- customThe crude was purified by flash chromatography on silica gel
Sources & evidence
- ORD record
- ord-5c080ca66af54f07991c6dedcba90f0a
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08846711B2
Reaction notes
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