Sulfuric Acid → 4-(3,4-Dimethoxyphenyl)-6-methyl-1,2,3,4-tetrahydroisoquinoline

HRID 2352252Notes

Reaction equation

HRID 2352252 reaction equation
[CH3:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][NH:7][CH2:8][CH:9](O)[C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=2)=[CH:4][CH:3]=1.S(=O)(=O)(O)O>FC(F)(F)C(O)=O>[CH3:19][O:18][C:12]1[CH:11]=[C:10]([CH:9]2[C:21]3[C:5](=[CH:4][CH:3]=[C:2]([CH3:1])[CH:22]=3)[CH2:6][NH:7][CH2:8]2)[CH:15]=[CH:14][C:13]=1[O:16][CH3:17]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 10590414alpha-[[(4-Methylbenzyl)amino]methyl]-3,4-dimethoxybenzyl alcohol

Product 1

HCID 106843994-(3,4-Dimethoxyphenyl)-6-methyl-1,2,3,4-tetrahydroisoquinolineYield 98.3%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

530 mg of α-[[(4-methylbenzyl)amino]methyl]-3,4-dimethoxybenzyl alcohol was dissolved in 4 ml of trifluoroacetic acid, and after adding thereto 0.12 ml of conc. sulfuric acid under ice cooling, the mixture was allowed to react for 30 minutes. The reaction solution was concentrated, and subjected to azeotropic distillation with toluene 2 times. After adding chloroform, the mixture was basified by addition of 28% aqueous ammonia. By a separating procedure, the chloroform layer was collected, was washed with water once, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was recrystallized from ethyl acetate-n-hexane, giving 490 mg of 4-(3,4-dimethoxyphenyl)-6-methyl-1,2,3,4-tetrahydroisoquinoline (melting point: 94°-96° C.). (2) To 450 mg of 4-(3,4-dimethoxyphenyl)-6-methyl-1,2,3,4-tetrahydroisoquinoline, was added 9 ml of 48% hydrobromic acid, and the mixture was heated under reflux under an argon gas stream for 3 hours. The reaction solution was cooled, and the crystals which separated out were collected by filtration, giving 390 mg of 4-(3,4-dihydroxyphenyl)-6 -methyl-1,2,3,4-tetrahydroisoquinoline hydrobromide.

Workup

  1. additionafter adding
  2. customto react for 30 minutes
  3. concentrationThe reaction solution was concentrated
  4. distillationsubjected to azeotropic distillation with toluene 2 times
  5. additionAfter adding chloroform
  6. additionthe mixture was basified by addition of 28% aqueous ammonia
  7. customBy a separating procedure, the chloroform layer was collected
  8. washwas washed with water once
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationThe solvent was distilled off
  11. customthe residue was recrystallized from ethyl acetate-n-hexane

Sources & evidence

ORD record
ord-ed653c298d584e76adb0d0a0add49139
Source dataset
uspto-grants-1989_10
Patent number
US04876261

Reaction notes

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