反应详情

To a suspension of N-(4-{2-[3-fluoro-4-(hydroxymethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide (118.8 mg, 0.4036 mmol) in anhydrous tetrahydrofuran (1.5 ml) was added 1,1′-carbonyldiimidazole (98.1 mg, 0.605 mmol), and the mixture was stirred at room temperature for 2.5 hr. tert-Butyl carbazate (160.3 mg, 1.213 mmol) was added, and the mixture was stirred at room temperature for 20 hr. Water, 1M hydrochloric acid and ethyl acetate were added, and the mixture was stirred, stood still and then partitioned. The organic layer was washed twice with water, and washed with saturated brine. After drying over anhydrous magnesium sulfate, the residue was concentrated under reduced pressure. The residue was suspended in dichloromethane (15 ml) and filtered. After washing with dichloromethane, the residue was dried under reduced pressure and purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 12 g, ethyl acetate:hexane=1:1). The fractions containing the object product were concentrated to give a solid, which was suspended in a mixture of tert-butyl methyl ether (5 ml) and hexane (5 ml) and filtered. The filtered product was dried under reduced pressure to give 4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}-2-fluorobenzyl tert-butyl hydrazine-1,2-dicarboxylate (153.7 mg, 0.340 mmol, yield 84.2%) as a white solid.

1. stirringthe mixture was stirred at room temperature for 20 hr
2. stirringthe mixture was stirred
3. custompartitioned
4. washThe organic layer was washed twice with water
5. washwashed with saturated brine
6. dry with materialAfter drying over anhydrous magnesium sulfate
7. concentrationthe residue was concentrated under reduced pressure
8. filtrationfiltered
9. washAfter washing with dichloromethane
10. customthe residue was dried under reduced pressure
11. custompurified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 12 g, ethyl acetate:hexane=1:1)
12. additionThe fractions containing the object product
13. concentrationwere concentrated
14. customto give a solid, which
15. filtrationfiltered
16. customThe filtered product was dried under reduced pressure