反应详情

4-(1′-Methanesulfonyl-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-5-yloxymethyl)-piperidine is suspended in 800 mL of methanol and added to an autoclave with a mechanical stirrer. 1500 mL of methanol are added and then dimethyloxirane (117 g, 1.62 mol) is added. The mixture is stirred at 60˜70° C. for 88 h, cooled to 25˜30° C. and concentrated to 1000 mL. The mixture is heated at 60˜70° C. and 4200 mL of water are added. The resulting mixture is stirred at 60˜70° C. during 30 min and cooled slowly to 0˜5° C. in 1.5˜2 h. It is stirred at this temperature for 30 minutes and filtered. The cake is slurried with H2O: MeOH=3:1 (600 mL) pre-cooled to 0˜5° C. and concentrated (2×). The product is dried under vacuum at 40˜50° C. to provide 320 g of off-white solid with 98.3% HPLC purity.

1. additionadded to an autoclave with a mechanical stirrer
2. temperaturecooled to 25˜30° C.
3. concentrationconcentrated to 1000 mL
4. temperatureThe mixture is heated at 60˜70° C.
5. addition4200 mL of water are added
6. stirringThe resulting mixture is stirred at 60˜70° C. during 30 min
7. temperaturecooled slowly to 0˜5° C. in 1.5˜2 h
8. stirringIt is stirred at this temperature for 30 minutes
9. filtrationfiltered
10. temperatureMeOH=3:1 (600 mL) pre-cooled to 0˜5° C.
11. concentrationconcentrated (2×)
12. customThe product is dried under vacuum at 40˜50° C.