反应详情

Synthesis of benzyl protected 1,2-HOPO acid (1,2-HOPOBn acid) (1-benzyloxy-6-carboxypyridin-2-one), from 6-hydroxypicolinic acid was performed as reported by Raymond et al. (J. Med. Chem., 45, 3963 (2002)) (yield=80%). 1,2-HOPOBn acid (760 mg, 3.1 mmol) was added to 50 ml THF and dissolved immediately to a slightly yellow solution. NHS (360 mg, 3.1 mmol) was added to this solution (no color change) and stirred under N2 for 30 mins. DCC (640 mg, 3.1 mmol) was then added to the flask (no color change) and stirred for 3 hrs under N2. Solution was vacuum filtered to remove DCU and 4-phenylbenzylamine (568 mg, 3.1 mmol) was added to clear bronze filtrate. The solution stirred o/n at RT under N2. The creamy yellow solution was rotovaped to dryness; the residue was dissolved in methylene chloride and washed with saturated sodium bicarbonate. The organic layer was dryed over magnesium sulfate and then rotovaped to dryness to an off-white residue. The residue was sonicated in a minimal amount of MeOH to remove any remaining DCU. The sonicate was rotovaped to dryness and oven dried for 3 hours to a white solid with a 71% yield. Deprotection of the benzyl group was carried out in a 1:1 mixture of HCl (40 ml) to glacial acetic acid (40 ml) for 5 days. The milky white solution was then rotovaped to dryness and washed 3 times with MeOH. The final white residue (20) was oven dried to a 91% yield.

1. customSynthesis of benzyl
2. dissolutiondissolved immediately to a slightly yellow solution
3. additionNHS (360 mg, 3.1 mmol) was added to this solution (no color change) and
4. stirringstirred for 3 hrs under N2
5. filtrationfiltered
6. stirringThe solution stirred o/n at RT under N2
7. washwashed with saturated sodium bicarbonate
8. customThe residue was sonicated in a minimal amount of MeOH
9. customto remove any remaining DCU
10. customdried for 3 hours to a white solid with a 71% yield
11. additionDeprotection of the benzyl group was carried out in a 1:1 mixture of HCl (40 ml) to glacial acetic acid (40 ml) for 5 days
12. washwashed 3 times with MeOH
13. customdried to a 91% yield