Sodium Carbonate → HCID 68683153, compound

Participants

Reaction Steps

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%).

Provenance & Evidence