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

HRID 452179Notes

Reaction equation

HRID 452179 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[C:9](#N)CC.P(Cl)([O:18][CH2:19][CH3:20])(OCC)=O.C(C1N(CC2[CH:53]=[CH:52][C:39]3/[C:40](=[CH:49]/[C:50]#[N:51])/[C:41]4[CH:48]=[CH:47][CH:46]=[CH:45]C=4C[CH2:44][C:38]=3C=2)C2=NC(C)=CC(C)=C2N=1)C.[C:54]([O:57][CH2:58]C)(=[O:56])[CH3:55]>C1COCC1.O>[CH3:58][O:57][C:54]([C:55]1[CH:53]=[CH:52][C:39]2=[C:38]([CH:44]=1)[O:18][CH2:19][C:20]1[CH:45]=[CH:46][CH:47]=[CH:48][C:41]=1/[C:40]/2=[C:49](/[C:50]#[N:51])\[CH3:1])=[O:56].[CH3:58][O:57][C:54]([C:55]1[CH:53]=[CH:52][C:39]2=[C:38]([CH:44]=1)[O:18][CH2:19][C:20]1[CH:45]=[CH:46][CH:47]=[CH:48][C:41]=1/[C:40]/2=[C:49](\[C:50]#[N:51])/[CH3:9])=[O:56]

Participants

9

Reactant 5

HCID 7854PropionitrileHCID 8857Ethyl AcetateHCID 13139Diethyl chlorophosphateHCID 2724682Lithium diisopropylamideHCID 22858094(E)-[2-(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene]acetonitrile

Product 2

HCID 67210386methyl (Z)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylateYield 37%HCID 67210387methyl (E)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylateYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

[step 1] Lithium diisopropylamide (2.0 mol/L heptane/THF/ethylbenzene solution, 100 mL, 200 mmol) was diluted with THF (40 mL), a solution of propiononitrile (7.13 mL, 100 mmol) in THF (40 mL) was added dropwise while stirring at 0° C. over 15 min. 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. To the mixture were added ethyl acetate and water, and the mixture was extracted with 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 (Z)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylic acid methyl ester (4.47 g, 14.6 mmol, 37%) and (E)-11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepine-3-carboxylic acid methyl ester (6.40 g, 21.0 mmol, 53%).

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 with 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-7a20a1e54c884dc39bfdbf6905780326
Source dataset
uspto-grants-2013_07
Patent number
US08486980B2

Reaction notes

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