反应详情

Ethyl 2-(acetylamino)-4-(2-{4-[(tert-butoxycarbonyl)amino]phenyl}ethyl)-1,3-thiazole-5-carboxylate (3 g), 1N-aqueous sodium hydroxide solution (17.3 ml) and ethanol (30 ml) were combined, and the mixture was refluxed for 5 hours. After cooled to room temperature, the organic solvent was removed in vacuo. The aqueous solution was acidified (pH=4) with 1N-hydrochloric acid, and extracted with ethyl acetate (twice). The combined organic layer was dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residual solid was dissolved in pyridine (45 ml), and then acetyl chloride (1.48 ml) was added dropwise to the solution at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 13 hours, and pyridine was removed in vacuo. Water was added to the residue, and acidified with 1N-hydrochloric acid. The precipitate was collected in vacuo. The solid was washed with water and ethyl ether to give 2-(acetylamino)-4-(2-{4-[(tert-butoxycarbonyl)amino]phenyl}ethyl)-1,3-thiazole-5-carboxylic acid (2.23 g) as an off-white solid.

1. temperaturethe mixture was refluxed for 5 hours
2. customthe organic solvent was removed in vacuo
3. extractionextracted with ethyl acetate (twice)
4. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
5. concentrationconcentrated in vacuo
6. dissolutionThe residual solid was dissolved in pyridine (45 ml)
7. additionacetyl chloride (1.48 ml) was added dropwise to the solution at 0° C. under nitrogen atmosphere
8. custompyridine was removed in vacuo
9. additionWater was added to the residue
10. customThe precipitate was collected in vacuo
11. washThe solid was washed with water and ethyl ether