Triphenylphosphine → 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid

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Reaction Conditions

Reaction Steps

5.57 g (15 mmol) of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3) was dissolved in 150 ml of abs. DMF/benzene (1:1). After the solution was degassed, under argon 1.18 g (4.5 mmol) of triphenylphosphine and 1.17 g (9 mmol) of Ca(HCO2)2 were added. After renewed flushing with argon, 867 mg (0.75 mmol) of Pd(PPh3)4 was added and carbon monoxide was passed into the solution. The mixture was stirred at 120° C. After six hours at 120° C. and standing overnight under argon, a further 867 mg (0.75 mmol) of Pd(PPh3)4 was added and stirring at 120° C. and passing carbon monoxide into the solution was continued for eight hours. After again standing overnight, 135 mg of PdCl2 was added and reaction was allowed to take place under the same conditions. For workup, the solvent was removed in vacuo and the residue was taken up in ethyl acetate. Three extractions with 2 N NaOH were carried out. The combined aqueous phases were adjusted to pH 6 with 6 N HCl and extracted three times with ethyl acetate. The organic phases were dried with MgSO4 and freed of solvent. The residue was purified on silica gel using a dichloromethane/methanol mixture, resulting in 420 mg of the title compound (Rt=4.025 min (method A); MS(Cl+)=336.1/338.1).

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