反应详情

A mixture of 450 mg of 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1yl]-pyridine (Production Example 1), 272 mg of 1-tert-butoxycarbonyl-3-ethynyl-3-piperidinol (Production Example 15), 63.6 mg of tetrakis(triphenylphosphine)palladium (0), 41.9 mg of copper (I) iodide, 460 μl of triethylamine, 5 ml of methanol and 1 ml of N,N-dimethyl formamide was heated under reflux under nitrogen atmosphere for 3 hours. After standing to cool, water, ethyl acetate, an aqueous ammonia chloride solution were added to the reaction mixture, and the organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and then the solvent was removed. To the residue were added 2 ml of trifluoroacetic acid and 2 ml of dichloromethane, followed by stirring at room temperature for 1 hour. The reaction mixture was neutralized with an aqueous sodium hydrogen carbonate solution and an organic layer was separated by adding ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and the solvent was removed. The residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate, to give 387 mg of the entitled compound.

1. temperaturewas heated
2. temperatureunder reflux under nitrogen atmosphere for 3 hours
3. temperatureto cool
4. washthe organic layer was washed with water and brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customthe solvent was removed
7. additionTo the residue were added 2 ml of trifluoroacetic acid and 2 ml of dichloromethane
8. customan organic layer was separated
9. additionby adding ethyl acetate
10. washThe organic layer was washed with brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customthe solvent was removed
13. customThe residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate