Acetic Acid → 2-Allyl-1-[1-(4-chlorophenyl)cyclobutyl]-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline oxalate

HRID 440490Notes

Reaction equation

HRID 440490 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:12]3[C:21]4[C:16](=[CH:17][C:18]([O:24]C)=[C:19]([O:22]C)[CH:20]=4)[CH2:15][CH2:14][NH:13]3)[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH2:26](Br)[CH:27]=[CH2:28].[C:30](=[O:33])([O-:32])[O-].[K+].[K+].Br.N.[C:38]([OH:41])(=[O:40])C>C(N(CC)CC)C.CC(C)=O>[C:38]([OH:41])(=[O:40])[C:30]([OH:32])=[O:33].[CH2:28]([N:13]1[CH2:14][CH2:15][C:16]2[C:21](=[CH:20][C:19]([OH:22])=[C:18]([OH:24])[CH:17]=2)[CH:12]1[C:8]1([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH2:11][CH2:10][CH2:9]1)[CH:27]=[CH2:26]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 222AmmoniaHCID 260Hydrogen BromideHCID 7841Allyl bromideHCID 11430Potassium CarbonateHCID 224067941-[1-(4-Chlorophenyl)cyclobutyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 224068812-Allyl-1-[1-(4-chlorophenyl)cyclobutyl]-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline oxalate

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 1-[1-(4-chlorophenyl)cyclobutyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (7.29 g prepared as described in Example 50), allyl bromide (2.66 g), anhydrous potassium carbonate (5.52 g) and acetone (100 ml) was heated under reflux for 2 hours. The reaction mixture was filtered and the solvent was removed by evaporation to give a residue which was digested with a 9:1 mixture of petroleum ether and triethylamine. The solution was decanted from a residual tar, filtered and the solvent removed to give a residue. A sample of this residue (3 g) was heated under reflux in a nitrogen atmosphere with glacial acetic acid (50 ml) and 48% hydrobromic acid (50 ml) for 7 hours. The reaction mixture was added to ice/water and excess aqueous ammonia solution added slowly under nitrogen. The resulting mixture was extracted with ethyl acetate. The organic layer was evaporated and the residue dissolved in ethyl acetate. Addition of a solution of oxalic acid in ethyl acetate gave 2-allyl-1-[1-(4 -chlorophenyl)cyclobutyl]-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline oxalate [m.p. 85° C. (dec)] which was dried in air.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 hours
  3. filtrationThe reaction mixture was filtered
  4. customthe solvent was removed by evaporation
  5. customto give a residue which
  6. customThe solution was decanted from a residual tar
  7. filtrationfiltered
  8. customthe solvent removed
  9. customto give a residue
  10. additionadded slowly under nitrogen
  11. extractionThe resulting mixture was extracted with ethyl acetate
  12. customThe organic layer was evaporated
  13. dissolutionthe residue dissolved in ethyl acetate
  14. additionAddition of a solution of oxalic acid in ethyl acetate

Sources & evidence

ORD record
ord-914cce8c49fb4f20bd3cbf6e1a8e1b61
Source dataset
uspto-grants-1996_05
Patent number
US05519034

Reaction notes

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