反应详情

A solution of 3-aminopicolinic acid (5.00 g, 36.2 mmol) in EtOH (70 mL) and concentrated sulfuric acid (6.0 mL, 110 mmol) was heated to 100° C. and stirred for 5 days. The cooled mixture was concentrated to −20 mL and poured over ice. This mixture was treated with aqueous ammonia (NH4OH, conc) until pH>7. This was extracted twice with 100 mL EtOAc. The basified aqueous layer was saturated with salt and extracted again with 2× 100 mL EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to 4.15 g of an off white solid (69%). 1H NMR (400 MHz, DMSO-d6) δ 1.30 (t, J=7.07 Hz, 3H), 4.27 (q, J=7.07 Hz, 2H), 6.67 (br. s., 2H), 7.17-7.22 (m, 1H), 7.24-7.29 (m, 1H), 7.84 (dd, J=4.04, 1.52 Hz, 1H). MS (ES+): m/z=167.06 (100) [M+1]. HPLC: tR=2.76 min (ZQ3, vvpolar—5 min).

1. concentrationThe cooled mixture was concentrated to −20 mL
2. additionpoured over ice
3. additionThis mixture was treated with aqueous ammonia (NH4OH, conc) until pH>7
4. extractionThis was extracted twice with 100 mL EtOAc
5. extractionextracted again with 2× 100 mL EtOAc
6. washThe combined organic layers were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated to 4.15 g of an off white solid (69%)
10. customHPLC: tR=2.76 min (ZQ3, vvpolar—5 min)