反应详情

温度

0 °C

To a stirred solution of tert-butyl 4-[5-(pyridin-2-ylethynyl)pyridin-2-yl]piperazine-1-carboxylate (3.8 g, 10.4 mmol) in CH2Cl2 (35 mL) at 0° C. was added trifluoroacetic acid (17.2 mL). The reaction was brought to room temperature and stirred for 30 minutes. Volatiles were removed in vacuo, and the residue was azeotroped with toluene (2×10 mL). The residue was then dissolved in CH2Cl2 and washed with aqueous sodium hydroxide solution (2M, 2×20 mL). The layers were then separated and the aqueous phase extracted with CH2Cl2 (3×10 mL). The combined organic extracts were then dried, (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in CH2Cl2 (50 mL), and cooled to 0° C. and treated sequentially with triethylamine (1.5 mL, 16.7 mmol) and methanesulfonyl chloride (1.1 mL, 13.5 mmol). The reaction was brought to RT and stirred for 1 hour. The reaction was then quenched with water (50 mL). The layers were separated and the aqueous phase extracted with CH2Cl2 (3×20 mL). The combined organic extracts were then dried, (MgSO4), filtered and concentrated in vacuo. The residue was then purified by flash chromatography (silica gel, 10% MeOH in EtoAc) to give 1-(methylsulfonyl)-4-[5-(pyridin-2-ylethynyl)pyridin-2-yl]piperazine as a brown solid (3.5 g, 10.2 mmol, 98%).

1. customwas brought to room temperature
2. customVolatiles were removed in vacuo
3. customthe residue was azeotroped with toluene (2×10 mL)
4. dissolutionThe residue was then dissolved in CH2Cl2
5. washwashed with aqueous sodium hydroxide solution (2M, 2×20 mL)
6. customThe layers were then separated
7. extractionthe aqueous phase extracted with CH2Cl2 (3×10 mL)
8. dry with materialThe combined organic extracts were then dried, (MgSO4),
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. dissolutionThe residue was dissolved in CH2Cl2 (50 mL)
12. customwas brought to RT
13. stirringstirred for 1 hour
14. customThe reaction was then quenched with water (50 mL)
15. customThe layers were separated
16. extractionthe aqueous phase extracted with CH2Cl2 (3×20 mL)
17. dry with materialThe combined organic extracts were then dried, (MgSO4),
18. filtrationfiltered
19. concentrationconcentrated in vacuo
20. customThe residue was then purified by flash chromatography (silica gel, 10% MeOH in EtoAc)