Hydrochloric Acid → 1-(2-Amino-4-chloro-3-fluorophenyl)-2-chloroethanone

To a stirred solution of AlCl3 (10.0 g, 75.01 mmol) and BCl3 (1M in n-hexane) (74 mL, 75.01 mmol) in CH2Cl2 (80 mL) was added 3-chloro-2-fluoroaniline 1 (9.0 g, 6.18 mmol) followed by a solution of chloroacetonitrile (11.6 g, 153.64 mmol) in CH2Cl2 (20 mL) at 0° C. under inert atmosphere. The reaction mixture was allowed to stir at RT for 30 minutes; heated to reflux temperature and maintained for additional 14 h. The reaction mixture was then cooled to 0° C., added aqueous 3N HCl solution (100 mL) and raised the temperature to reflux and stirred for 3 h. After completion of the reaction by TLC, the reaction mixture was cooled RT, diluted with water (50 mL) and extracted with CH2Cl2 (2×150 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified by triturating with n-pentane to afford compound 2 (4.5 g, 33%) as an off-white solid. 1H NMR (500 MHz, DMSO-d6): δ 7.61 (d, J=9.0 Hz, 1H), 7.35 (br s, 2H), 6.72 (d, J=9.0 Hz, 1H), 5.06 (s, 2H).

1. temperatureheated
2. temperatureto reflux temperature
3. temperaturemaintained for additional 14 h
4. temperatureThe reaction mixture was then cooled to 0° C.
5. temperatureraised the temperature
6. temperatureto reflux
7. stirringstirred for 3 h
8. customAfter completion of the reaction by TLC
9. temperaturethe reaction mixture was cooled RT
10. extractionextracted with CH2Cl2 (2×150 mL)
11. dry with materialThe combined organic extracts were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customto obtain the crude
15. customThe crude was purified
16. customby triturating with n-pentane

ORD record

ord-3989b6cf34c34e0da4378e66501e8ad7

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09334261B2