1,2-dihydroisoquinoline → 1,2,3,4-Tetrahydroisoquinoline

HRID 2358017Notes

Reaction equation

HRID 2358017 reaction equation
N[C@H](C1C=CC=CC=1)[C@H](NS(C1C(C)=CC(C)=CC=1C)(=O)=O)C1C=CC=CC=1.[CH2:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][NH:30]1.C([O-])(O)=O.[Na+]>C(#N)C.ClCCl.CC1C=CC(C(C)C)=CC=1.CC1C=CC(C(C)C)=CC=1.Cl[Ru]Cl.Cl[Ru]Cl.C(N(CC)CC)C.C(O)=O>[CH2:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31][NH:30]1

Participants

9

Reactant 3

HCID 4225111,2-dihydroisoquinolineHCID 516892Sodium BicarbonateHCID 12165385(1R,2R)-N-(2,4,6-trimethylphenylsulfonyl)-1,2-diphenylethane-1,2-diamine

Product 1

HCID 70461,2,3,4-Tetrahydroisoquinoline

Reagents, catalysts & solvents 5

HCID 10908223Dichloro(p-cymene)ruthenium(II) dimerCatalystHCID 284Formic AcidSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
80 °C

Procedure

Dichloro-(p-cymene)ruthenium (II) dimer (0.20 mmol) is added to a solution of N-((1R,2R)-2-amino-1,2-diphenyl-ethyl)-2,4,6-trimethylbenzene-sulfonamide (0.40 mmol) and triethylamine (0.80 mmol) in acetonitrile (3.0 mL). The mixture is stirred for 1 h at 80° C. and added to a solution of the respective dihydroisoquinoline (28.0 mmol) in dichloromethane (30 mL). An azeotropic mixture of formic acid and triethylamine (5:2, 14 mL) is added (gas evolution). After 90 min a sat. aqueous NaHCO3 solution (200 mL) is added to the dark red solution. The layers are separated, the aqueous layer is extracted twice with DCM (2×200 mL) and the combined organic extracts are concentrated in vacuo. The residue is dissolved in isopropanol (1600 mL) and treated with a solution of HCl in isopropanol (5-6 M, 10 mL). The obtained hydrochloride salt is recrystallized to give the respective 1,2,3,4-tetrahydroisoquinoline with high enantiomeric excess as determined by chiral HPLC. The hydrochloride salt is converted to the free base by extraction with sat. NaHCO3 solution/dichloromethane. The absolute configuration of the respective product is assigned in analogy to the literature (N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996, 118, 4916-4917).

Workup

  1. additionis added (gas evolution)
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted twice with DCM (2×200 mL)
  4. concentrationthe combined organic extracts are concentrated in vacuo
  5. dissolutionThe residue is dissolved in isopropanol (1600 mL)
  6. additiontreated with a solution of HCl in isopropanol (5-6 M, 10 mL)
  7. customThe obtained hydrochloride salt is recrystallized

Sources & evidence

ORD record
ord-b5850045484344c39c4374516ba63869
Source dataset
uspto-grants-2010_07
Patent number
US07763638B2

Reaction notes

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