Sodium hydride → 5-(3-(tetrahydropyran-2-yloxy)-1propyl)-10,11dihydro-5H-dibenzo[a,d]cycloheptene-5-carbonitrile

HRID 2293952Notes

Reaction equation

HRID 2293952 reaction equation
[H-].[Na+].[CH:3]1[C:13]2[CH2:12][CH2:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[CH:8]([C:18]#[N:19])[C:7]=2[CH:6]=[CH:5][CH:4]=1.[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][CH2:27][CH2:28][CH2:29]Br>C1(C)C=CC=CC=1>[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][CH2:27][CH2:28][CH2:29][C:8]1([C:18]#[N:19])[C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[CH2:11][CH2:12][C:13]2[CH:3]=[CH:4][CH:5]=[CH:6][C:7]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27779882-(3-Bromopropoxy)tetrahydro-2H-pyranHCID 1409111110,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carbonitrile

Product 1

HCID 187993365-(3-(tetrahydropyran-2-yloxy)-1propyl)-10,11dihydro-5H-dibenzo[a,d]cycloheptene-5-carbonitrileYield 99%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
50 °C

Procedure

In a 50 ml roundbottom flask equipped with magnetical stirring, thermometer and addition funnel, sodium hydride (0.8 g, 0.02 mol, 60% dispersion in oil) was suspended in dry toluene under an atmosphere of nitrogen. A solution of 10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carbonitrile (3.0 g, 0.014 mol, prepared in a similar way as described in J. Med. Chem., 6, (1963), 251) in dry toluene (15 ml) was added. The reaction mixture was heated to reflux temperature in 30 minutes and then heated at reflux temperature for 150 minutes. After cooling to about 50° C., a solution of 3-bromopropyl tetrahydropyranyl ether (4.5 g, 0.02 mol) in dry toluene (6 ml) was added dropwise. The reaction mixture was heated at reflux temperature for 5 h and then left stirring at room temperature overnight. After filtration of precipitated salts, the solution was washed with 1N HCl (100 ml), diluted with more toluene (100 ml) and finally washed with water. After drying (MgSO4), the organic phase was evaporated in vacuo affording 7.2 g (99%) of 5-(3-(tetrahydropyran-2-yloxy) -1-propyl)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carbonitrile.

Workup

  1. customIn a 50 ml roundbottom flask equipped with magnetical stirring
  2. additionthermometer and addition funnel
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux temperature in 30 minutes
  5. temperatureheated
  6. temperatureat reflux temperature for 150 minutes
  7. temperatureThe reaction mixture was heated
  8. temperatureat reflux temperature for 5 h
  9. waitleft
  10. filtrationAfter filtration of precipitated salts
  11. washthe solution was washed with 1N HCl (100 ml)
  12. additiondiluted with more toluene (100 ml)
  13. washfinally washed with water
  14. dry with materialAfter drying (MgSO4)
  15. customthe organic phase was evaporated in vacuo

Sources & evidence

ORD record
ord-4edbcb78496f41e8ac427063e56f3ba4
Source dataset
uspto-grants-1997_11
Patent number
US05688788

Reaction notes

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