反应详情

温度

40 °C

The mixture of N-(t-butoxycarbonyl)-4-amino-L-phenylalanine methylester(10.25 g), 2-amino-5-iodobenzoic acid (9.18 g), EDC/HCl (6.8 g), HOBT (4.8 g), triethylamine (6.6 mL) and tetrahydrofuran (300 mL) was stirred at 40° C. overnight. The solution wherein about a half amount of the solvent was removed was diluted with water and ethyl acetate and liquid separation was conducted. The organic layer was washed with water, saturated aqueous solution of ammonium chloride, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was removed to obtain 22 g of the crude material. The crude material (22 g), CDI (carbonyldiimidazole) (17 g) and DMF (200 mL) were stirred at 80° C. overnight. The reaction solution was diluted with water and ethyl acetate, and liquid separation was conducted. The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was removed to obtain 23.4 g of the crude material. The crude material (23.4 g), methyl iodide (3 mL), potassium carbonate (10.0 g) and DMF (100 mL) were stirred at room temperature overnight. The reaction solution was diluted with water and ethyl acetate, and liquid separation was conducted. The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was removed to obtain 15 g of the intended compound.

1. customThe solution wherein about a half amount of the solvent was removed
2. additionwas diluted with water and ethyl acetate and liquid separation
3. washThe organic layer was washed with water, saturated aqueous solution of ammonium chloride, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride
4. dry with materialdried over anhydrous sodium sulfate
5. customThe solvent was removed
6. customto obtain 22 g of the crude material
7. washThe organic layer was washed with water
8. dry with materialdried over anhydrous sodium sulfate
9. customThe solvent was removed
10. customto obtain 23.4 g of the crude material
11. washThe organic layer was washed with water
12. dry with materialdried over anhydrous sodium sulfate
13. customThe solvent was removed