Phosphorus oxychloride → 7-Methoxy-1-methyl-3,4-dihydroisoquinoline

HRID 6754

Reaction equation

HRID 6754 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][NH:16][C:17](=O)[CH3:18])=[CH:10][CH:9]=1>C(#N)C>[CH3:6][O:7][C:8]1[CH:13]=[C:12]2[C:11]([CH2:14][CH2:15][N:16]=[C:17]2[CH3:18])=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 584258N-(2-(4-Methoxyphenyl)ethyl)acetamide

Product 1

HCID 150619777-Methoxy-1-methyl-3,4-dihydroisoquinolineYield 45.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

Phosphorus oxychloride (22.5 mL) was added to a solution of N-[2-(4-methoxy-phenyl)-ethyl]-acetamide (6.5 g) in acetonitrile (200 mL). The mixture was heated at 120° C. in a sealed tube for 16 h. The solvent was evaporated. The residue was dissolved in dichloromethane (200 mL) and washed with aqueous sodium bicarbonate (saturated, 100 mL) and brine (100 mL). The dichloromethane layer was dried over sodium sulfate, filtered and evaporated. The crude product was purified by column chromatography (5% methanol in dichloromethane) to afford 7-methoxy-1-methyl-3,4-dihydro-isoquinoline (2.67 g).

Workup

  1. customThe solvent was evaporated
  2. dissolutionThe residue was dissolved in dichloromethane (200 mL)
  3. washwashed with aqueous sodium bicarbonate (saturated, 100 mL) and brine (100 mL)
  4. dry with materialThe dichloromethane layer was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by column chromatography (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-30b35afd736244dbb5dcce6e7edbcd5b
Source dataset
uspto-grants-2006_08
Patent number
US07084154B2

Linked notes

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