反应详情

Boc-Glu-OtBu (100 mg, 0.33 mmol) and HATU (150.4 mg, 0.40 mmol) were dissolved in 2 mL of DMF. Triethylamine (68.5 μL) was added thereto and stirred for 10 minutes. Ethyl 3-aminobenzoate (49.2 mg, 0.33 mmol) was added thereto and stirred overnight. After liquid separation was conducted with an ethyl acetate and an aqueous solution of 1M sodium hydroxide, the organic layer was washed with an aqueous solution of 1M sodium hydroxide, 1M hydrochloric acid and a saturated saline solution, successively, and dried with sodium sulfate to remove a solvent. The obtained residue was dissolved in 2 mL of THF, 1 mL of ethanol and 1 mL of water, and lithium hydroxide monohydrate (13.5 mg, 0.32 mmol) was added thereto. After stirring the mixture for 5 hours, 4.5 mg of lithium hydroxide was added thereto and stirred overnight. After confirming the completion of the reaction, pH of the reaction solution was adjusted to 2 with 1M hydrochloric acid, and a solvent was removed therefrom. 3 mL of TFA was added to the obtained residue and stirred at room temperature for 5 hours. After removing a solvent, purification was conducted in accordance with the purification process A to obtain a title compound.

1. stirringstirred overnight
2. customAfter liquid separation
3. washan aqueous solution of 1M sodium hydroxide, the organic layer was washed with an aqueous solution of 1M sodium hydroxide, 1M hydrochloric acid
4. dry with materiala saturated saline solution, successively, and dried with sodium sulfate
5. customto remove a solvent
6. dissolutionThe obtained residue was dissolved in 2 mL of THF
7. stirringAfter stirring the mixture for 5 hours
8. stirringstirred overnight
9. customthe completion of the reaction, pH of the reaction solution
10. customa solvent was removed
11. addition3 mL of TFA was added to the obtained residue
12. stirringstirred at room temperature for 5 hours
13. customAfter removing
14. customa solvent, purification