反应详情

The intermediate 1-(4-Benzo[b]thiophen-2-yl-benzyl)-6,7-dimethoxy-8-methyl-3,4-dihydro-1-H-isoquinoline-2-carboxylic acid tert-butyl ester (21) was prepared as follows: A mixture of 0.462 g (1 mmol) of 1-(4-Bromo-benzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester and 0.270 g (1.5 mol. equiv.) of thianaphthene-2-boronic acid in 4 ml of isopropanol was stirred under argon at room temperature for 30 min. 1 mg (0.45 mol %) of palladium(II)acetate, 4 mg (1.3 mol %) of triphenylphosphine, and 0.6 ml (1.2 mol. equiv.) of 2M sodium bicarbonate aqueous solution were added successively and the mixture was refluxed with stirring for 6 hours. The solvent was evaporated under reduced pressure and the residue was partitioned between 50 ml of ethyl acetate and 25 ml of 5% sodium hydroxide aqueous solution. After shaking, the organic layer was washed with water (25 ml) and brine (25 ml), and then dried with sodium sulfate. The solvent was evaporated under reduced pressure and the remaining oil was crystallized by trituration with n-hexanes. The solid was recrystallized using ethyl acetate n-hexanes mixture to give 0.41 g (78%) of white solid, mp 137-139° C.

1. temperaturethe mixture was refluxed
2. stirringwith stirring for 6 hours
3. customThe solvent was evaporated under reduced pressure
4. customthe residue was partitioned between 50 ml of ethyl acetate and 25 ml of 5% sodium hydroxide aqueous solution
5. stirringAfter shaking
6. washthe organic layer was washed with water (25 ml) and brine (25 ml)
7. dry with materialdried with sodium sulfate
8. customThe solvent was evaporated under reduced pressure
9. customthe remaining oil was crystallized by trituration with n-hexanes
10. customThe solid was recrystallized