Acetonitrile → HCID 178430885, compound

Temperature

140 °C

To a 350 mL pressure vessel was added 4-methylimidazole (17.85 g, 217 mmol, 1 eq.) and a stirbar. Acetonitrile (53 mL, 1022 mmol, 4.7 eq.) was added. Triethylamine (88 mL, 631 mmol, 2.9 eq.) was added and the mixture was stirred until it became homogeneous. 3-Fluorobenzoylchloride (100 g, 631 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 hours 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 (250 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 refluxed at 85° C. for 1 hour. The mixture was allowed to cool slightly and then was filtered through a Celite pad followed by a rinse with 1N HCl (˜200 mL). The filtrate was made alkaline with NH4OH 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 ketone 3 as an off-white solid (30.0 g, 80%). LC/MSD (HP Series 1100 MSD) Expected MW: 204.07, Observed M+H: 205.0, Retention time: 1.48. Analytical HPLC: >95% purity, retention time: 3.00 (8 minute run) 1H NMR, DMSO-d6, Varian 400 MHz δ 13.10 (br s, 1H), 8.28 (m, 2H), 7.60 (m, 1H), 7.52 (m, 1H), 7.30-7.06 (d, 1H), 2.29 (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 (250 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 refluxed at 85° C. for 1 hour
13. temperatureto cool slightly
14. filtrationwas filtered through a Celite pad
15. washa rinse with 1N HCl (˜200 mL)
16. customformed
17. filtrationThe solid was filtered
18. washwashed with copious amounts of dilute NH4OH
19. customto remove triethylamine hydrochloride salts
20. customThe solid was collected

ORD record

ord-3f7a81b03b8340098456bcbc68890149

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07626031B2