Acetic Acid → HCID 87262159, compound

Temperature

-78 °C

To a solution of 3-Chloro-4-fluoro-benzotrifluoride (5.0 g, 25.18 mmol) in THF (40 ml) was added at −78° C. n-BuLi (1.6 M in hexanes, 16.53 ml, 26.45 mmol, 1.05 equiv.) over a period of ca. 20 min. The clear yellow solution was stirred for 15 min at −78° C. and then transferred dropwise via cannula to a pre-cooled (−78° C.) solution of DMF (2.14 ml, 27.7 mmol, 1.1 equiv.) in THF (100 ml) such as that the internal temperature stayed below −65° C. The light yellow reaction mixture was stirred for 2 h at −78° C., was then warmed to 0° C. and quenched upon addition of a acetic acid (4.32 g, 75.54 mmol, 3.0 equiv.) and water (50 ml) keeping the temperature below 5° C. The turbid light yellow suspension was stirred for 2 h, the precipitate was filtered off with suction on a funnel with a fritted disk and the filter cake was washed with TBME (30 ml). The organic phase was separated and washed with water (50 ml), whereas the aqueous phase was washed with TBME (50 ml). The combined organic phases were dried over sodium sulfate, filtered and the solvents were removed under vacuum and the residue was treated with toluene (40 ml) and a solution of sodium pyrosulfite (5.42 g, 27.95 mmol, 1.11 equiv.) in water (12 ml) was added, whereupon a white suspension was formed. The suspension was stirred overnight (ca. 15 h), the precipitate was filtered off, washed with toluene (20 ml) and dried under vacuum to yield the title compound as a light yellow crystalline compound (7.82 g, 93.9% yield).

1. customstayed below −65° C
2. stirringThe light yellow reaction mixture was stirred for 2 h at −78° C.
3. temperaturewas then warmed to 0° C.
4. customthe temperature below 5° C
5. stirringThe turbid light yellow suspension was stirred for 2 h
6. filtrationthe precipitate was filtered off with suction on a funnel with a fritted disk
7. washthe filter cake was washed with TBME (30 ml)
8. customThe organic phase was separated
9. washwashed with water (50 ml), whereas the aqueous phase
10. washwas washed with TBME (50 ml)
11. dry with materialThe combined organic phases were dried over sodium sulfate
12. filtrationfiltered
13. customthe solvents were removed under vacuum
14. additionthe residue was treated with toluene (40 ml)
15. customwas formed
16. stirringThe suspension was stirred overnight (ca. 15 h)
17. filtrationthe precipitate was filtered off
18. washwashed with toluene (20 ml)
19. customdried under vacuum

ORD record

ord-3cd8c2e679594827a34e91a5d4a0ca7d

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329939B2