反应详情

温度

0 °C

Add 2.0 M Al(CH3)3 (1.28 mL, 2.56 mmol) to a suspension of 5-(4-chloro-phenyl)-3-trimethylsilanylethynyl-thiophene-2-carboxylic acid methyl ester (0.851 g, 2.44 mmol) and 3-(4-amino-2-fluoro-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (0.688 g, 2.44 mmol) in toluene (20 mL). Stir the reaction at 60° C. for 4 h. Cool the mixture to 0° C., quench with 2.0 M NaOH (5 mL) and water (20 mL) and then extract with CHCl3 (3×50 mL). Dry with Na2SO4, filter, and concentrate. Dissolve the crude material in THF (50 mL), treat with 1.0 M TBAF (2.93 mL, 2.93 mmol) and stir at RT overnight. Dilute with EtOAc (100 mL), wash with water (3×40 mL), dry with Na2SO4, filter, and concentrate. Purify the crude material by chromatography, eluting with 5% CH3OH/CHCl3 to give 1.03 g (80%) of the title compound. LC-MS/ES m/z (35Cl) 526.9 [M+H]+.

1. customthe reaction at 60° C. for 4 h
2. customquench with 2.0 M NaOH (5 mL) and water (20 mL)
3. extractionextract with CHCl3 (3×50 mL)
4. dry with materialDry with Na2SO4
5. filtrationfilter
6. concentrationconcentrate
7. dissolutionDissolve the crude material in THF (50 mL)
8. stirringstir at RT overnight
9. washwash with water (3×40 mL)
10. dry with materialdry with Na2SO4
11. filtrationfilter
12. concentrationconcentrate
13. customPurify the crude material by chromatography
14. washeluting with 5% CH3OH/CHCl3