反应详情

4-bromo-2-chloro-5-fluoro-benzoic acid (Apollo Scientific; 5.0 g, 19.8 mmol) was added to DMF (250 mL), to this was added HBTU (9.8 g, 25.7 mmol), N-methyl-4-aminopiperidine (Fluorochem; 2.5 g, 21.8 mmol) and DIPEA (7.0 mL, 39.5 mmol). The reaction was stirred overnight, evaporated to dryness, quenched with 2.0 N NaOH (100 mL), extracted with DCM (3×100 mL), dried and solvent removed in vacuo. The residue was dissolved in hot acetonitrile, allowed to cool filtered, and the filtrate passed through a SCX column and the residue, after evaporation of product containing fractions, recrystallised from hot acetonitrile to yield the title compound as a white solid (5.0 g, 82%).

1. customevaporated to dryness
2. customquenched with 2.0 N NaOH (100 mL)
3. extractionextracted with DCM (3×100 mL)
4. customdried
5. customsolvent removed in vacuo
6. dissolutionThe residue was dissolved in hot acetonitrile
7. temperatureto cool
8. filtrationfiltered
9. customthe residue, after evaporation of product
10. additioncontaining fractions
11. customrecrystallised from hot acetonitrile