反应详情

Borane-tetrahydrofuran complex solution (1 M in THF, 132 mL, 132 mmol) was added dropwise over 30 min at 0-5° C. to a solution of 3-chloro-4-fluoro-phenylacetonitrile (4.37 g, 25.8 mmol) in THF (40 mL), then the reaction mixture was stirred at RT for 20 min and refluxed for 21 h. The reaction mixture was then cooled to 0° C., and methanol (30 mL) was added at 2-5° C. over 45 minutes. After refluxing for 1 h the reaction mixture was concentrated, the residue dissolved in dichloromethane and the amine extracted twice with 1 M aq. hydrochloric acid solution. The combined aqueous phases were then treated with concentrated aq. sodium hydroxide solution to adjust the pH to 12, then extracted twice with dichloromethane. The combined organic phases were washed with water, dried over magnesium sulfate, filtered and concentrated, leading to a colorless oil (4.3 g). This was dissolved in diethyl ether (125 mL), treated with hydrogen chloride solution (2.6 M in diethyl ether), and stirred at RT for 1 h. The precipitate was then collected by filtration to afford the title compound (3.93 g, 73%) White solid, MS (ISP) 174.1 (M−Cl)+.

1. temperaturerefluxed for 21 h
2. temperatureThe reaction mixture was then cooled to 0° C.
3. temperatureAfter refluxing for 1 h the reaction mixture
4. concentrationwas concentrated
5. dissolutionthe residue dissolved in dichloromethane
6. extractionthe amine extracted twice with 1 M aq. hydrochloric acid solution
7. additionThe combined aqueous phases were then treated with concentrated aq. sodium hydroxide solution
8. extractionextracted twice with dichloromethane
9. washThe combined organic phases were washed with water
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. dissolutionThis was dissolved in diethyl ether (125 mL)
14. additiontreated with hydrogen chloride solution (2.6 M in diethyl ether)
15. stirringstirred at RT for 1 h
16. filtrationThe precipitate was then collected by filtration