Succinic Acid → Solifenacin Succinate

関与物質

反応手順

127.2 g (1.0 mol) of (R)-quinuclidinol was dissolved in 1270 mL of dichloromethane and then stirred at 25˜30° C. for 20 minutes to obtain a reaction solution. Subsequently, 472.9 g (1.2 mol) of bis(pentafluorophenyl)carbonate was added to the reaction solution to form a suspended reaction solution, and then the suspended reaction solution was stirred at 25˜30° C. for 3˜4 hours. After confirming the completion of a reaction using thin layer chromatography (TLC), the reaction solution was concentrated under reduced pressure. Subsequently, oily matter obtained by adding 1270 mL of isopropanol to the reaction solution was dissolved, and then 209.3 g (1.0 mol) of (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline was added to the reaction solution and stirred at 25˜30° C. for 4˜5 hours. After confirming the completion of a reaction using high performance liquid chromatography (HPLC), the reaction solution was concentrated under reduced pressure. Subsequently, 1270 mL water was added to the reaction solution, and concentrated hydrochloric acid was added dropwise into the reaction solution to adjust the pH of the reaction solution to 1˜2. Then, the reaction solution was washed with 1270 mL of toluene to remove pentafluorophenol (a by-product formed during the reaction) from the reaction product. Then, an aqueous layer was extracted from the reaction solution using 1270 mL of dichloromethane, and then the reaction solution was concentrated under reduced pressure. Then, 1270 mL of water was added to the reaction solution, the pH of the reaction solution was adjusted to 9˜10 using ammonium hydroxide, and then an aqueous layer was further extracted from the reaction solution using 1270 mL of toluene. Subsequently, 1270 mL of acetone and 118.1 g (1.0 mol) of succinic acid were added to the reaction solution, stirred at 55˜60° C. for 30 minutes, further stirred at 10˜15° C. for 2 hours, and then filtered to obtain a reaction product. Finally, the reaction product was washed with 640 mL of toluene and 640 mL of acetone, and then dried in vacuum at 40° C. to obtain 386.4 g (80.4%) of solifenacin succinate.

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