Acetonitrile → HCID 178430884, compound

Temperature

140 °C

To a 350 mL pressure vessel was added 4-methylimidazole (12 g, 146 mmol, 1 eq.) and a stirbar. Acetonitrile (35 mL, 670 mmol, 4.6 eq.) was added. Triethylamine (59 mL, 424 mmol, 2.9 eq.) was added and the mixture was stirred until it became homogeneous. 2-fluorobenzoyl chloride (67.2 g, 424 mmol, 2.9 eq.) was added. Upon addition of the acyl chloride, the mixture became warm and viscous. The vessel was sealed and heated at 140° C. for 2 h with stirring. During heating, the mixture turned black in color. The vessel was removed from the heat, allowed to cool, and its contents were diluted with acetone (50 mL). The mixture was stirred and transferred to a 2 L round-bottomed flask containing 7% aqueous HCl (1000 mL). Charcoal was added to the flask and the mixture was heated at reflux for 1.5 h. The mixture was allowed to cool almost to room temperature and then was filtered through a Celite pad followed by a rinse with 1N HCl (˜100 mL). The filtrate was placed in an ice bath and was made alkaline with aqueous NH4OH (35%) whereupon a solid precipitate formed. The solid was filtered and washed with copious amounts of dilute NH4OH to remove triethylamine hydrochloride salts. The solid was collected and placed under high vacuum, yielding the desired ketone 1 as a brown solid (20.1 g, 67%). LC/MSD (HP Series 1100 MSD) Expected MW: 204.07, Observed M+H: 205.0, Retention time: 1.13. 1H NMR, CD3OD, Varian 400 MHz δ 7.70 (t, 1H), 7.59 (m, 1H), 7.30 (t, 1H), 7.25-6.96 (m, 2H), 2.34 (s, 3H).

1. temperaturethe mixture became warm
2. customThe vessel was sealed
3. stirringwith stirring
4. temperatureDuring heating
5. customThe vessel was removed from the heat
6. temperatureto cool
7. additionits contents were diluted with acetone (50 mL)
8. stirringThe mixture was stirred
9. customtransferred to a 2 L round-bottomed flask
10. additioncontaining 7% aqueous HCl (1000 mL)
11. additionCharcoal was added to the flask
12. temperaturethe mixture was heated
13. temperatureat reflux for 1.5 h
14. temperatureto cool almost to room temperature
15. filtrationwas filtered through a Celite pad
16. washa rinse with 1N HCl (˜100 mL)
17. customThe filtrate was placed in an ice bath
18. customformed
19. filtrationThe solid was filtered
20. washwashed with copious amounts of dilute NH4OH
21. customto remove triethylamine hydrochloride salts
22. customThe solid was collected

ORD record

ord-2c4e6efcf3854e609c84cc6ee3e8309f

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07626031B2