反应详情

温度

0 °C

1.87 g of (3-chloro-2-fluoro-phenyl)-acetonitrile (11 mmol) were dissolved in 18 ml THF and cooled down to 0° C. under nitrogen. 58 ml of a 1M borane-THF complex solution in THF (58 mmol) were then added dropwise over 20 min by keeping the temperature between 0 to 2° C. After addition the reaction mixture was stirred at rt for additional 20 min, and refluxed for 21 h. The reaction mixture was then cooled down to 0° C. and treated between 2 and 5° C. with 13 ml methanol over a period of 35 min. After 1 h refluxing the reaction mixture was concentrated, the residue dissolved in DCM and the amine extracted twice with 1N aqueous HCl. The combined aqueous phases were then treated with concentrated NaOH to adjust the pH to 12, and then extracted twice with DCM. The combined organic phases were then washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo leading to 1.6 g colorless oil. This was dissolved in 50 ml diethylether, treated with 5 ml 2.6N HCl in diethylether, stirred at rt for additional 60 min, filtered and dried under high vacuo, leading to 1.6 g white solid (69%). MS (ISP) 174.2 (M+H)+.

1. custombetween 0 to 2° C
2. additionAfter addition the reaction mixture
3. temperaturerefluxed for 21 h
4. temperatureThe reaction mixture was then cooled down to 0° C.
5. temperatureAfter 1 h refluxing the reaction mixture
6. concentrationwas concentrated
7. dissolutionthe residue dissolved in DCM
8. extractionthe amine extracted twice with 1N aqueous HCl
9. additionThe combined aqueous phases were then treated with concentrated NaOH
10. extractionextracted twice with DCM
11. washThe combined organic phases were then washed with water
12. dry with materialdried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. dissolutionThis was dissolved in 50 ml diethylether
16. additiontreated with 5 ml 2.6N HCl in diethylether
17. stirringstirred at rt for additional 60 min
18. filtrationfiltered
19. customdried under high vacuo