2-Bromobenzonitrile → 4-[(2'-Cyanobiphenyl-4-yl)methoxy]-2-ethyl-5,6,7,8-tetrahydroquinoline

HRID 5681

Reaction equation

HRID 5681 reaction equation
[CH2:1]([C:3]1[CH:12]=[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=2)[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]=1)[CH3:2].Br[C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[C:27]#[N:28]>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([C:26]1[CH:29]=[CH:30][CH:31]=[CH:32][C:25]=1[C:18]1[CH:19]=[CH:20][C:15]([CH2:14][O:13][C:11]2[C:10]3[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=3[N:4]=[C:3]([CH2:1][CH3:2])[CH:12]=2)=[CH:16][CH:17]=1)#[N:28]

Participants

6

Reactant 2

HCID 162722-BromobenzonitrileHCID 151714224-[(2-Ethyl-5,6,7,8-tetrahydroquinolin-4-yl)oxymethyl]phenylboronic acid

Product 1

HCID 197964084-[(2'-Cyanobiphenyl-4-yl)methoxy]-2-ethyl-5,6,7,8-tetrahydroquinolineYield 49.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 10340Sodium CarbonateSolvent

Procedure

Tetrakis(triphenylphosphine)palladium (40 mg) was added to a suspension of 4-[(2-ethyl-5,6,7,8-tetrahydroquinolin-4-yl)oxymethyl]-phenylboronic acid (200 mg) and 2-bromobenzonitrile (106 mg) in toluene (2 ml) ethanol (0.5 ml) and 2M aqueous sodium carbonate (0.58 ml). The mixture was degassed and placed under an atmosphere of argon, then heated under reflux for 12 hours. The resulting solution was cooled to ambient temperature, and dichloromethane (30 ml) and water (10 ml) were added. The organic layer was separated, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography, eluting with ethyl acetate/hexane (3:1 v/v), and the product triturated with ether/hexane to give 4-[(2'-cyanobiphenyl-4-yl)methoxy]-2-ethyl-5,6,7,8-tetrahydroquinoline (106 mg) as a white solid, m.p. 147°-148° C.; NMR (CDCl3): 1.29(t,3H), 1.7-1.95(m,4H), 5.17(s,2H), 6.57(s,1H), 7.4-7.7 (complex m,7 H), 7.78(d,1H); mass spectrum (+ve CI) 369 (M+H)+.

Workup

  1. customThe mixture was degassed
  2. temperatureheated
  3. temperatureunder reflux for 12 hours
  4. additiondichloromethane (30 ml) and water (10 ml) were added
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe residue was purified by flash chromatography
  9. washeluting with ethyl acetate/hexane (3:1 v/v)
  10. customthe product triturated with ether/hexane

Sources & evidence

ORD record
ord-f2e47c7899134a9295da63016e60ddb0
Source dataset
uspto-grants-1993_09
Patent number
US05245035

Linked notes

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