反应详情

A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (500 mg), 5-hydroxypyridine-3-carboxylic acid (287 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (403 mg), 1-hydroxy-1H-benzotriazole monohydrate (322 mg), triethylamine (0.488 mL), and N,N-dimethylformamide (5 mL) was stirred at room temperature for 16 h. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to provide a powder (LC/MS (ESI+) m/z: 340 (M+H)+). A mixture of the powder, tert-butyl bromoacetate (683 mg), potassium carbonate (691 mg), and N,N-dimethylformamide (10 mL) was stirred at 60° C. for 5 h. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography (silica gel, 90:10-50:50 hexane/ethyl acetate) to provide the title compound (530 mg, 68%) as crystals.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe ethyl acetate layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. customto provide a powder (LC/MS (ESI+) m/z: 340 (M+H)+)
6. stirringwas stirred at 60° C. for 5 h
7. extractionthe mixture was extracted with ethyl acetate
8. washThe ethyl acetate layer was washed with saturated brine
9. dry with materialdried over anhydrous magnesium sulfate
10. customThe solvent was evaporated under reduced pressure
11. customthe residue was purified by flash column chromatography (silica gel, 90:10-50:50 hexane/ethyl acetate)