Diisopropylethylamine → HCID 58181341, compound

To a solution of 2,6-dichloro-3-(trifluoromethyl)pyridine (2.38 g, 11.0 mmol) in anhydrous dichloromethane (20 ml) was added dropwise N,N-diisopropylethylamine (3.7 ml, 225 mmol). A solution of 1-acetylpiperazine (1.69 g, 13.2 mmol) in anhydrous dichloromethane (10 ml) was added dropwise at 0° C., and the mixture was stirred at room temperature for 5 hrs. The mixture was warmed, heated under reflux for 2.5 hrs, and stirred at room temperature for 14 hrs. The reaction mixture was diluted with dichloromethane and washed with water. The aqueous layer was extracted twice with dichloromethane, and the combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4→ethyl acetate→ethanol:ethyl acetate=1:20) to give 1-acetyl-4-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazine (451 mg, yield 13%) as a yellow solid.

1. temperatureThe mixture was warmed
2. temperatureheated
3. temperatureunder reflux for 2.5 hrs
4. stirringstirred at room temperature for 14 hrs
5. washwashed with water
6. extractionThe aqueous layer was extracted twice with dichloromethane
7. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4→ethyl acetate→ethanol:ethyl acetate=1:20)

ORD record

ord-b10d2b4e6a6c42bbb32cc8ed99b08478

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08999989B2