Citric Acid → HCID 87262159, compound

Temperature

-78 °C

To a solution of 3-Chloro-4-fluoro-benzotrifluoride (20.0 g, 100.7 mmol) in THF (200 ml) was added at −78° C. n-BuLi (1.6 M in hexanes, 66.1 ml, 105.7 mmol, 1.05 equiv.) over a period of ca. 20 min. The clear yellow solution was stirred for 30 min at −78° C. and a solution of DMF (8.54 ml, 110.8 mmol, 1.1 equiv.) in THF (100 ml) was added dropwise, such as that the internal temperature stayed below −70° C. The light yellow reaction mixture was stirred for 3 h at −78° C. and was then warmed to 0° C. At this temperature the reaction mixture was quenched upon addition of a solution of citric acid (58.13 g, 302.1 mmol, 3.0 equiv.) in water (400 ml) keeping the temperature below 5° C. The organic phase was separated and washed with water (300 ml), whereas the aqueous phase was washed with TBME (300 ml). The combined organic phases were dried over sodium sulfate, the solvents were removed under vacuum and the residue was treated with toluene (200 ml), whereupon a white precipitate was formed. The suspension was stirred for 15 min, the precipitate was filtered off and the mother liquor was treated by dropwise addition of a solution of sodium pyrosulfite (21.68 g, 111.8 mmol, 1.11 equiv.) in water (60 ml), whereupon a white suspension was formed. The suspension was stirred overnight (ca. 15 h), the precipitate was filtered off, washed with toluene (100 ml) and dried under vacuum to yield the title compound as a off-white crystalline compound (32.54 g, 97.7% yield). MS (EI): m/z 306.9 ([M−H]−, 100%). 1H-NMR (DMSO, 300 MHz): δ 8.00-7.85 (m, 2H), 6.58 (d, 1H), 5.31 (d, 1H).

1. customstayed below −70° C
2. stirringThe light yellow reaction mixture was stirred for 3 h at −78° C.
3. temperaturewas then warmed to 0° C
4. customthe temperature below 5° C
5. customThe organic phase was separated
6. washwashed with water (300 ml), whereas the aqueous phase
7. washwas washed with TBME (300 ml)
8. dry with materialThe combined organic phases were dried over sodium sulfate
9. customthe solvents were removed under vacuum
10. additionthe residue was treated with toluene (200 ml), whereupon a white precipitate
11. customwas formed
12. stirringThe suspension was stirred for 15 min
13. filtrationthe precipitate was filtered off
14. customwas formed
15. stirringThe suspension was stirred overnight (ca. 15 h)
16. filtrationthe precipitate was filtered off
17. washwashed with toluene (100 ml)
18. customdried under vacuum

ORD record

ord-d79f5279aa874062986ad174bfae6c1f

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329939B2