Ammonia → 3-[3-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl)-3-pyridyl]propyloxy]pyrrolidine

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A mixture of 742 mg of 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridine (Production Example 1), 389 mg of 1-benzyl-3-(2-propynyloxy)pyrrolidine (Production Example 16), 62.7 mg of tetrakis(triphenylphosphine)palladium (0), 51.7 mg of copper (I) iodide, 757 μl of triethylamine, 4 ml of methanol and 4 ml of N,N-dimethylformamide was stirred under nitrogen atmosphere at 75° C. for 2 hours. After standing to cool, water, ethyl acetate and aqueous ammonia were added to the reaction mixture. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, filtered through NH-silica gel and the solvent was removed. After 10 ml of methanol, 1 ml of acetic acid and 50 mg of 10% palladium carbon were added to the residue and hydrogen substitution was performed, the mixture was stirred at room temperature overnight. After the reaction mixture was nitrogen-purged, it was filtered through Celite. The solvent was removed, and then the residue was purified by silica gel column chromatography with ethyl acetate/methanol/aqueous ammonia (100/5/2), to give 465 mg of the title compound.

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