Acrylonitrile → (S)-3-(5-(1-methylpyrrolidin-2-yl)pyridin-3-yl)acrylonitrile
Reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[CH3:13])[CH:7]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.[C:43](#[N:46])[CH:44]=[CH2:45]>CC#N.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:13][N:9]1[CH2:10][CH2:11][CH2:12][C@H:8]1[C:6]1[CH:7]=[C:2]([CH:45]=[CH:44][C:43]#[N:46])[CH:3]=[N:4][CH:5]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of (S)-3-bromo-5-(1-methylpyrrolidin-2-yl)pyridine (preparation 1) (300 mg, 1.24 mmol), palladium (II) acetate (14 mg, 0.06 mmol), tri(o-tolyl)phosphine (75 mg, 0.25 mmol) and triethylamine (0.35 mL, 2.48 mmol) in MeCN (10 mL) was degassed by bubbling argon through. Acrylonitrile (0.12 mL, 1.87 mmol) was then added and the reaction mixture heated at reflux temperature for 18 hours. The reaction mixture was cooled to room temperature, filtered through Celite, and the solvents evaporated to give a brown solid. The crude product was purified by flash chromatography (2% [20% ammonia in MeOH] in DCM) to give the title compound as a red-brown oil (188 mg, 71%, mixture of cis and trans isomers).
Workup
- customwas degassed
- customby bubbling argon through
- temperaturethe reaction mixture heated
- temperatureat reflux temperature for 18 hours
- filtrationfiltered through Celite
- customthe solvents evaporated
- customto give a brown solid
- customThe crude product was purified by flash chromatography (2% [20% ammonia in MeOH] in DCM)
Sources & evidence
- ORD record
- ord-d47365aea8fe49dc9f7d4fc444655bff
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08980276B2
Reaction notes
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