Potassium Hydroxide → 7-Methoxy-1-methyl-3,4-dihydroisoquinoline

HRID 1932302Notes

Reaction equation

HRID 1932302 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][NH:25][C:26](=O)[CH3:27])=[CH:19][CH:18]=1.P(Cl)(Cl)(Cl)=O.[OH-].[K+]>>[CH3:15][O:16][C:17]1[CH:22]=[C:21]2[C:20]([CH2:23][CH2:24][N:25]=[C:26]2[CH3:27])=[CH:19][CH:18]=1

Participants

5

Reactant 4

HCID 14797Potassium HydroxideHCID 14812Phosphorus oxide (P4O10)HCID 24813Phosphorus oxychlorideHCID 584258N-(2-(4-Methoxyphenyl)ethyl)acetamide

Product 1

HCID 150619777-Methoxy-1-methyl-3,4-dihydroisoquinolineYield 32.5%

Procedure

Phosphorus pentoxide (22 g, 155.24 mmol) was added to a mixture of N-[2-(4-methoxyphenyl)-ethyl]-acetamide (50 g, 258.73 mmol) prepared in Step 1 and phosphorus oxychloride (48 ml, 517.46 mmol). The reaction mixture was refluxed for 3 hours. The reaction mixture was cooled to room temperature, added to ice water, basified with 2N potassium hydroxide solution, and then extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried on anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography to give 14.72 g of the titled compound as brown oil. (Yield: 32%) The product was used in the subsequent step without further purification.

Workup

  1. temperatureThe reaction mixture was refluxed for 3 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with a saturated sodium chloride solution
  4. dry with materialdried on anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified with silica gel column chromatography

Sources & evidence

ORD record
ord-c6f48d4bae1345ff94ec73f96323bcaa
Source dataset
uspto-grants-2012_05
Patent number
US08188114B2

Reaction notes

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