1,2,3,4-Tetrahydroisoquinoline → 6,7-Dimethoxy-3',4'-dihydro-1'H-[1,2']biisoquinolinyl

HRID 915824Notes

Reaction equation

HRID 915824 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl[C:48]1[C:57]2[C:52](=[CH:53][C:54]([O:60][CH3:61])=[C:55]([O:58][CH3:59])[CH:56]=2)[CH:51]=[CH:50][N:49]=1.[CH2:62]1[C:71]2[C:66](=[CH:67][CH:68]=[CH:69][CH:70]=2)[CH2:65][CH2:64][NH:63]1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:61][O:60][C:54]1[CH:53]=[C:52]2[C:57](=[CH:56][C:55]=1[O:58][CH3:59])[C:48]([N:63]1[CH2:64][CH2:65][C:66]3[C:71](=[CH:70][CH:69]=[CH:68][CH:67]=3)[CH2:62]1)=[N:49][CH:50]=[CH:51]2

Participants

9

Reactant 4

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 634876Binap, (A+-)-HCID 106407081-Chloro-6,7-dimethoxyisoquinolineHCID 23665647Potassium tert-butoxide

Product 1

HCID 116454496,7-Dimethoxy-3',4'-dihydro-1'H-[1,2']biisoquinolinylYield 87.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Palladium acetate (25 mg 0.112 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (209 mg, 0.335 mmol) were heated to 80° C. in toluene (25 mL) for 20 min. To the mixture was added 500 mg (2.24 mmol) of 1-chloro-6,7-dimethoxy-isoquinoline, 298 mg (2.24 mmol) of tetrahydroisoquinoline, and 4.47 mL (4.47 mmol) of a 1.0 M solution of potassium tert-butoxide in THF. After stirring at reflux for 4 h, the mixture was diluted with EtOAc, washed with water, dried over MgSO4 and concentrated. Silica gel chromatography (4:1 hexanes/EtOAc) provided 625 mg (87%) of the title compound as a yellow oil. The hydrochloride salt (387 mg) was obtained after treatment with concd. HCl in isopropanol and recrystallization from EtOH/MeOH.

Workup

  1. temperatureat reflux for 4 h
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-c8e4a677f4f343f5b97cae2753885fd8
Source dataset
uspto-grants-2007_09
Patent number
US07268142B2

Reaction notes

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