Hydrochloric Acid → (Z)-2-(2-hydroxymethyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propiononitrile

HRID 885420Notes

Reaction equation

HRID 885420 reaction equation
[H-].[Na+].[C:3]([CH:5](P(=O)(OCC)OCC)[CH3:6])#[N:4].O=[C:16]1[C:22]2[CH:23]=[CH:24][C:25]([C:27](OCC)=[O:28])=[CH:26][C:21]=2[CH2:20][CH2:19][C:18]2[CH:32]=[CH:33][CH:34]=[CH:35][C:17]1=2.[BH4-].[Li+].Cl>CN(C=O)C.C1COCC1.O>[OH:28][CH2:27][C:25]1[CH:24]=[CH:23][C:22]2/[C:16](=[C:5](\[CH3:6])/[C:3]#[N:4])/[C:17]3[CH:35]=[CH:34][CH:33]=[CH:32][C:18]=3[CH2:19][CH2:20][C:21]=2[CH:26]=1.[OH:28][CH2:27][C:25]1[CH:24]=[CH:23][C:22]2/[C:16](=[C:5](/[CH3:6])\[C:3]#[N:4])/[C:17]3[CH:35]=[CH:34][CH:33]=[CH:32][C:18]=3[CH2:19][CH2:20][C:21]=2[CH:26]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 282103Diethyl (1-cyanoethyl)phosphonateHCID 4148881Lithium borohydrideHCID 67211051ethyl 10,11-dihydro-5-oxo-5H-dibenzo[a,d]cycloheptene-2-carboxylate

Product 2

HCID 67210308(Z)-2-(2-hydroxymethyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propiononitrileYield 27%HCID 67210474(E)-2-(2-hydroxymethyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propiononitrileYield 27%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

[step 2] To a solution of sodium hydride (60%, 0.856 g, 21.4 mmol) and diethyl 1-cyanoethylphosphonate (4.09 g, 21.4 mmol) in DMF (35 mL), a solution of ethyl 10,11-dihydro-5-oxo-5H-dibenzo[a,d]cycloheptene-2-carboxylate (3.0 g, 10.7 mmol) obtained in step 1 in DMF (10 mL) was added under ice-cooling, and the mixture was stirred at 80° C. for 3 hr. Water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a residue. The obtained residue was dissolved in THF (50 mL), followed by adding lithium borohydride (1.11 g, 50.9 mmol) and the mixture was stirred at 50° C. for 5 hr. The mixture was neutralized with 2 mol/L hydrochloric acid, and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/ethyl acetate=98/2) to give (E)-2-(2-hydroxymethyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propiononitrile (0.730 g, 27%) and (Z)-2-(2-hydroxymethyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propiononitrile (0.728 g, 27%), respectively.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto give a residue
  6. stirringthe mixture was stirred at 50° C. for 5 hr
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (chloroform/ethyl acetate=98/2)

Sources & evidence

ORD record
ord-e0126e0f4ac54487adcc436efcc21d2e
Source dataset
uspto-grants-2012_08
Patent number
US08242151B2

Reaction notes

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