反应详情

温度

8 °C

Treat 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride hydrate (Form II) (20.0 g, 0.0355 mol) with deionized water (2 g) and add acetone (60 mL) in small portions over several minutes with stirring. Filter through filter aid and wash the filter cake with acetone (30 mL). Wash the filtercake with acetone (22 mL), reflux filtrate and then slowly add ethyl acetate (32 mL over 15 minutes) keeping the mixture at reflux. Reflux for 10 minutes, then slowly add additional ethyl acetate (23 mL over 10 minutes) and reflux for an additional 15 minutes. Add additional ethyl acetate (60 mL over 5-10 minutes) and continue refluxing for 15 minutes. Cool to approximately 8° C. in an ice bath, filter the solid and wash with ethyl acetate (85 mL). Vacuum dry at 55° C. for 1.5 hours to give the title compound (18.16 g, 95%).

1. filtrationFilter
2. filtrationthrough filter aid
3. washwash the filter cake with acetone (30 mL)
4. washWash the filtercake with acetone (22 mL)
5. temperaturereflux filtrate
6. customslowly add ethyl acetate (32 mL over 15 minutes)
7. temperatureat reflux
8. temperatureReflux for 10 minutes
9. temperatureslowly add additional ethyl acetate (23 mL over 10 minutes) and reflux for an additional 15 minutes
10. additionAdd additional ethyl acetate (60 mL over 5-10 minutes)
11. temperaturecontinue refluxing for 15 minutes
12. filtrationfilter the solid
13. washwash with ethyl acetate (85 mL)
14. customVacuum dry at 55° C. for 1.5 hours