Hydrochloric Acid → 3-(L-gamma-glutamylamino)benzoic acid

Boc-Glu-OtBu (100 mg, 0.33 mmol) and HATU (150.4 mg, 0.40 mmol) were dissolved in 2 ml of DMF, and triethylamine (68.5 μl) was added to the solution. The mixture was then stirred for 10 minutes. Ethyl 3-aminobenzoate (49.2 mg, 0.33 mmol) was added to the mixture and stirred overnight. After liquid separation was effected with ethyl acetate and 1M aqueous sodium hydroxide solution, the organic layer was washed sequentially with 1M aqueous sodium hydroxide solution, 1M hydrochloric acid and aqueous saturated sodium chloride solution (brine), followed by drying over sodium sulfate. After the solvent was distilled off, the resulting residue was dissolved in 2 ml of THF, 1 ml of ethanol and 1 ml of water. Lithium hydroxide monohydrate (13.5 mg, 0.32 mmol) was added to the solution. After stirring for 5 hours, 4.5 mg of lithium hydroxide was added to the mixture and stirred overnight. After it was confirmed that the reaction was completed, pH of the reaction solution was adjusted to 2 with 1M hydrochloric acid and the solvent was distilled off. After 3 ml of TFA was added to the resulting residue, the mixture was stirred at room temperature for 5 hours and the solvent was removed by distillation. The mixture was then purified according to the purification step A to give the title compound.

1. stirringstirred overnight
2. customAfter liquid separation
3. washthe organic layer was washed sequentially with 1M aqueous sodium hydroxide solution, 1M hydrochloric acid and aqueous saturated sodium chloride solution (brine)
4. dry with materialby drying over sodium sulfate
5. distillationAfter the solvent was distilled off
6. dissolutionthe resulting residue was dissolved in 2 ml of THF
7. stirringAfter stirring for 5 hours
8. stirringstirred overnight
9. distillationthe solvent was distilled off
10. additionAfter 3 ml of TFA was added to the resulting residue
11. stirringthe mixture was stirred at room temperature for 5 hours
12. customthe solvent was removed by distillation
13. customThe mixture was then purified
14. customaccording to the purification step A

ORD-Eintrag

ord-e414fda7fda14477ab66d05810074d51

Quelldatensatz

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08877739B2