Hydrochloric Acid → 1-(2-Amino-4-chlorophenyl)ethanone

Temperature

0 °C

A 2 liter three neck flask equipped with an addition funnel, an argon inlet, and an overhead mechanical stirrer was charged with 2-amino-4-chlorobenzonitrile (15 g, 0.098 mol) and anhydrous diethyl ether (1.2 L). The reaction flask was back-filled with argon gas. The mixture was then cooled to 0° C. in an ice water bath. At this time, the reaction was treated with a solution of methyl magnesium chloride (3.0 M in tetrahydrofuran, 100 mL, 0.30 mol). The addition process occurred over 90 min. At this time, the reaction mixture was stirred at 0° C. for an additional 90 min. The reaction was then warmed to 25° C. and was stirred at 25° C. for 20 min. At this time, the reaction mixture was cooled to −60° C. using a dry ice/acetone bath and was then treated slowly dropwise with a 6N aqueous hydrochloric acid solution (100 mL). The reaction mixture was then allowed to warm to 18° C. with stirring over the course of 3 h. At this time, the reaction was treated with an additional amount of the 6N aqueous hydrochloric acid solution (100 mL). At this time, the reaction mixture was transferred to a separatory funnel. The organic layer was separated and set aside. The aqueous layer was brought to pH 9 by the slow addition of solid potassium hydroxide with stirring. The resulting mixture was then extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 1-(2-amino-4-chlorophenyl)ethanone (16.1 g, 96%) as a tan solid. This material was used without further purification.

1. additionThe reaction flask was back-filled with argon gas
2. temperatureThe reaction was then warmed to 25° C.
3. stirringwas stirred at 25° C. for 20 min
4. temperatureAt this time, the reaction mixture was cooled to −60° C.
5. temperatureto warm to 18° C.
6. stirringwith stirring over the course of 3 h
7. customAt this time, the reaction mixture was transferred to a separatory funnel
8. customThe organic layer was separated
9. additionThe aqueous layer was brought to pH 9 by the slow addition of solid potassium hydroxide
10. stirringwith stirring
11. extractionThe resulting mixture was then extracted with ethyl acetate
12. dry with materialThe combined organic layers were dried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-eab8cfbe6ff54bb8b0286516e8ec1803

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08471027B2