Propionitrile → methyl (E)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylate

HRID 885427Notes

Reaction equation

HRID 885427 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[C:9](#[N:12])[CH2:10][CH3:11].P(Cl)(OCC)([O:15][CH2:16]C)=O.O=[C:23]1[C:29]2[CH:30]=[CH:31][C:32]([C:34]([OH:36])=[O:35])=[CH:33][C:28]=2CC[C:25]2[CH:37]=[CH:38][CH:39]=[CH:40][C:24]1=2>C1COCC1.O.C(OCC)(=O)C>[C:9](/[C:10](=[C:23]1/[C:29]2[CH:30]=[CH:31][C:32]([C:34]([O:36][CH3:1])=[O:35])=[CH:33][C:28]=2[O:15][CH2:16][C:25]2[CH:37]=[CH:38][CH:39]=[CH:40][C:24]/1=2)/[CH3:11])#[N:12].[C:9](/[C:10](=[C:23]1\[C:29]2[CH:30]=[CH:31][C:32]([C:34]([O:36][CH3:1])=[O:35])=[CH:33][C:28]=2[O:15][CH2:16][C:25]2[CH:37]=[CH:38][CH:39]=[CH:40][C:24]\1=2)/[CH3:11])#[N:12]

Participants

9

Reactant 4

HCID 7854PropionitrileHCID 13139Diethyl chlorophosphateHCID 2724682Lithium diisopropylamideHCID 125258755-Oxo-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-2-carboxylic acid

Product 2

HCID 67210386methyl (Z)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylateYield 36.7%HCID 67210387methyl (E)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylateYield 52.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

[step 1] Lithium diisopropylamide (2.0 mol/L heptane/THF/ethylbenzene solution, 100 mL, 200 mmol) was diluted with THF (40 mL), and a solution of propiononitrile (7.13 mL, 100 mmol) in THF (40 mL) was added dropwise at 0° C. over 15 min with stirring. After stirring at 0° C. for 30 min, a solution of diethyl chlorophosphate (14.4 mL, 100 mmol) in THF (40 mL) was added dropwise over 45 min. After stirring at room temperature for 2 hr, methyl 11-oxo-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylate (JP-B-2526005, 10.7 g, 40 mmol) was added, and the mixture was stirred at room temperature for 1.5 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=15:85) to give methyl (E)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylate (6.40 g, 21.0 mmol, 52.6%) and methyl (Z)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylate (4.47 g, 14.6 mmol, 36.7%).

Workup

  1. stirringAfter stirring at 0° C. for 30 min
  2. stirringAfter stirring at room temperature for 2 hr
  3. stirringthe mixture was stirred at room temperature for 1.5 hr
  4. extractionthe mixture was extracted 3 times with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=15:85)

Sources & evidence

ORD record
ord-bd9566a184c541de9b0b68342e449b9f
Source dataset
uspto-grants-2012_08
Patent number
US08242151B2

Reaction notes

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