Trifluoroacetic acid → HCID 9888710, compound

Temperature

5 °C

The BOC-protected product of Example 11 (15 g) was dissolved in dichloromethane (75 ml) and the solution cooled to 5° C. Trifluoroacetic acid (48.7 g) was added dropwise maintaining the internal temperature at <10° C. The reaction mixture was then heated to 30° C. and aged for ca. 2 hours. The reaction mixture was then cooled to 0° C. and a 2M solution of sodium hydroxide was added dropwise maintaining the temperature at or below ambient. The resulting solution was allowed to settle for ca. 1 hour and the layers separated. The aqueous layer was treated with Ecosorb™ C-941 (0.75 g) at ambient temperature for 1 hour. The resulting mixture was filtered through a bed of Hyflo™. The filter-bed was washed with water (10 ml). The combined filtrates were acidified to pH 6.0 by adding concentrated hydrochloric acid (ca. 8 ml) whilst maintaining the temperature at or below ambient temperature. The aqueous solution was extracted with dichloromethane (2×150 ml) and the organics washed with water (50 ml). The solution was solvent switched to isopropanol (65 ml) at atmospheric pressure and the solution warmed to 40° C., seeded with 0.6% w/w seed, and maintained at 40° C. for 12 hours. Heating was then removed and the slurry allowed to cool to 20° C. Isolation by filtration and washing with isopropanol (3×15 ml) afforded the title compound (9.0g, 74% yield).

1. temperaturemaintaining the internal temperature at <10° C
2. temperatureThe reaction mixture was then heated to 30° C. and aged for ca. 2 hours
3. temperatureThe reaction mixture was then cooled to 0° C.
4. temperaturemaintaining the temperature at or below ambient
5. customthe layers separated
6. additionThe aqueous layer was treated with Ecosorb™ C-941 (0.75 g) at ambient temperature for 1 hour
7. filtrationThe resulting mixture was filtered through a bed of Hyflo™
8. washThe filter-bed was washed with water (10 ml)
9. additionby adding concentrated hydrochloric acid (ca. 8 ml)
10. temperaturewhilst maintaining the temperature at or below ambient temperature
11. extractionThe aqueous solution was extracted with dichloromethane (2×150 ml)
12. washthe organics washed with water (50 ml)
13. temperaturethe solution warmed to 40° C.
14. temperaturemaintained at 40° C. for 12 hours
15. temperatureHeating
16. customwas then removed
17. temperatureto cool to 20° C
18. filtrationIsolation by filtration
19. washwashing with isopropanol (3×15 ml)

ORD record

ord-67df8f8a869d45af9d1ff1e8fd11f20a

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07288655B2