Sodium Carbonate → HCID 68683153, compound

HRID 2238359Notes

Reaction equation

HRID 2238359 reaction equation
[ClH:1].Br[C:3]1[CH:23]=[CH:22][C:6]([CH2:7][CH:8]2[C:17]3[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=3)[CH2:11][CH2:10][NH:9]2)=[CH:5][CH:4]=1.[OH-].[Na+].[CH3:26][O:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+].O.O.C(O)(=O)C(O)=O>CC([O-])=O.CC([O-])=O.[Pd+2].C(Cl)Cl>[ClH:1].[CH3:21][O:20][C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][C:15]=1[O:18][CH3:19])[CH:8]([CH2:7][C:6]1[CH:22]=[CH:23][C:3]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([O:27][CH3:26])[CH:33]=3)=[CH:4][CH:5]=1)[NH:9][CH2:10][CH2:11]2

Participants

9

Reactant 6

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 61373Oxalic acid dihydrateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 68683499HCID 68683499, compound

Product 1

HCID 68683153HCID 68683153, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

6,7-dimethoxy-1-(3′-methoxy-biphenyl-4-ylmethyl)-1,2,3,4-tetrahydro-isoquinoline hydrochloride (35) was prepared as follows: 1-(4-bromo-benzyl)-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline hydrochloride (0.403 g, 1.01 mmol) was added to a mixture of 20 mL CH2Cl2 and 20 ml of 1N NaOH. The reaction mixture was stirred at room temperature. After dissolving of precipitate, the organic phase was separated, dried over Na2SO4, filtered, and evaporated. A residue was dissolved in 5 mL i-PrOH and 3-methoxy-phenyl-boronic acid (0.170 g, 1.12 mmol) was added. The resulting solution was stirred for 30 min at room temperature. Pd(OAc)2 (3 mg, 0.0134 mmol), PPh3 (8 mg, 0.0305 mmol) and 2N Na2CO3 (0.7 mL, 1.4 mmol) were added, the reaction mixture was refluxed for 6 h under Ar and evaporated. A residue was dissolved in chloroform and washed with 1N NaOH. The organic phase was dried under Na2SO4, filtered, and evaporated. A residue was dissolved in MeOH, and a solution of oxalic acid dihydrate (0.264 g, 2.08 mmol) was added under reflux. Oxalic acid salt was crystallized from McOH-Et2O mixture. Oxalic acid salt was added to a mixture of 20 mL CH2Cl2 and 20 ml of 1N NaOH. The reaction mixture was stirred at room temperature. After dissolving of precipitate, the organic phase was separated, dried over Na2SO4, filtered, and evaporated. A residue was dissolved in MeOH and 5 mL of 1M solution of IICl in Et2O was added. Hydrochloride was crystallized from the MeOH-Et2O mixture. Yield is 0.245 g (56.9%).

Workup

  1. dissolutionAfter dissolving of precipitate
  2. customthe organic phase was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionA residue was dissolved in 5 mL i-PrOH
  7. stirringThe resulting solution was stirred for 30 min at room temperature
  8. temperaturethe reaction mixture was refluxed for 6 h under Ar
  9. customevaporated
  10. dissolutionA residue was dissolved in chloroform
  11. washwashed with 1N NaOH
  12. customThe organic phase was dried under Na2SO4
  13. filtrationfiltered
  14. customevaporated
  15. dissolutionA residue was dissolved in MeOH
  16. temperatureunder reflux
  17. customOxalic acid salt was crystallized from McOH-Et2O mixture
  18. additionOxalic acid salt was added to a mixture of 20 mL CH2Cl2 and 20 ml of 1N NaOH
  19. stirringThe reaction mixture was stirred at room temperature
  20. dissolutionAfter dissolving of precipitate
  21. customthe organic phase was separated
  22. dry with materialdried over Na2SO4
  23. filtrationfiltered
  24. customevaporated
  25. dissolutionA residue was dissolved in MeOH
  26. addition5 mL of 1M solution of IICl in Et2O was added
  27. customHydrochloride was crystallized from the MeOH-Et2O mixture

Sources & evidence

ORD record
ord-b54af43c4cf6414e89558e0d83d7ce82
Source dataset
uspto-grants-2010_05
Patent number
US07718672B2

Reaction notes

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