反应详情

温度

200 °C

To a solution of 3-fluoro-2-(3,3,5,5-tetramethylcyclohex-1-enyl)phenylamine (623 mg, 2.52 mmol) produced in Example (97c) in 1,2-dichlorobenzene (7 mL) was added bis(2-chloroethyl)amine hydrochloride (560 mg, 3.14 mmol), followed by reflux for 5 hours at an external temperature of 200° C. under a nitrogen atmosphere. During the reaction, a nitrogen stream was circulated into the reactor several times to remove the hydrogen chloride gas. After cooling the reaction mixture to room temperature, ethyl acetate, tetrahydrofuran, methanol, saturated aqueous solution of sodium carbonate and water were added for partition between oil and water. The aqueous layer was further extracted with ethyl acetate, and the combined organic layer was dried over anhydrous sodium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 214 mg of the title compound as a light brown oil.

1. customDuring the reaction
2. customto remove the hydrogen chloride gas
3. temperatureAfter cooling the reaction mixture to room temperature
4. additionethyl acetate, tetrahydrofuran, methanol, saturated aqueous solution of sodium carbonate and water were added
5. customfor partition between oil and water
6. extractionThe aqueous layer was further extracted with ethyl acetate
7. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
8. filtrationThe desiccant was filtered off
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)