1,2,3,4-Tetrahydroisoquinoline → 2,3-Dihydro-2,4,6,7-tetramethyl-2-[(1,2,3,4-tetrahydroisoquinolin-2-yl)methyl]-5-benzofuranamine

HRID 565669Notes

Reaction equation

HRID 565669 reaction equation
Br[CH2:2][C:3]1([CH3:16])[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1.[CH2:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][NH:18]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.O>[CH3:16][C:3]1([CH2:2][N:18]2[CH2:19][CH2:20][C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:17]2)[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1

Participants

6

Reactant 3

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 11430Potassium CarbonateHCID 108505902-Bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine

Product 1

HCID 221110212,3-Dihydro-2,4,6,7-tetramethyl-2-[(1,2,3,4-tetrahydroisoquinolin-2-yl)methyl]-5-benzofuranamine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

A suspension of 2-bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine (1.4 g), 1,2,3,4-tetrahydroisoquinoline (1.3 g), and potassium carbonate (1.4 g) in N,N-dimethylacetamide (10 mL) was refluxed under nitrogen gas for 15 hours. This reaction mixture was diluted with water and extracted with 2 portions of ethyl acetate. The pooled organic layer was washed with water and saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3:1) to provide 2,3-dihydro-2,4,6,7-tetramethyl-2-[(1,2,3,4-tetrahydroisoquinolin-2-yl)methyl]-5-benzofuranamine. This product was dissolved in ethanol, followed by addition of 1 equivalent of oxalic acid solution in ethanol. This mixture was heated and the resulting solution was concentrated under reduced pressure. The crystals that separated out were collected to provide 1.5 g of the title compound. Yield 68%.

Workup

  1. temperaturewas refluxed under nitrogen gas for 15 hours
  2. extractionextracted with 2 portions of ethyl acetate
  3. washThe pooled organic layer was washed with water and saturated aqueous NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=3:1)

Sources & evidence

ORD record
ord-584265c8f22d41e3b9127368a6c45b06
Source dataset
uspto-grants-2001_01
Patent number
US06172085B2

Reaction notes

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