反应详情

A suspension of ethyl 3-aminopicolinate (Compound 6F, 4.15 g, 25.0 mmol) in H2O (30.0 mL) was treated with enough sulfuric acid to enable dissolution (˜1 mL). 2 mL of the total 10.7 mL of acetic acid to be used in this reaction was added in order to make the reaction mixture mostly homogeneous. A solution of bromine (1.29 mL, 25.0 mmol) in the remaining AcOH (8.7 mL) was added drop-wise to the vigorously stirring reaction mixture forming an orange precipitate. The mixture was allowed to stir for 15 min. The resulting thick yellow-orange suspension was filtered to collect a yellow precipitate. The filtrate was neutralized with saturated aqueous K2CO3 and the additional precipitate that formed was collected by filtration and combined with the previously collected precipitate. The combined precipitates were dried and re-crystallized in EtOH (overnight in the dark) to isolate 4.24 g of pale orange crystals. The mother liquor was purified on an ISCO Combiflash system eluting with 0-5% MeOH/DCM. To isolate a further 0.58 g of the desired product for a total of 4.82 g (79%). 1H NMR (400 MHz, DMSO-d6) δ 1.30 (t, J=7.1 Hz, 3H), 4.29 (q, J=7.1 Hz, 2H), 6.90 (br. s., 2H), 7.21 (d, J=8.6 Hz, 1H), 7.44 (d, J=8.8 Hz, 1H). MS (ESI): m/z 244.94 (100), 246.92 (100) [M+H]+. HPLC: tR=3.45 min (ZQ3: polar—5 min).

1. dissolutiondissolution (˜1 mL)
2. additionwas added in order
3. customreaction mixture
4. customforming an orange precipitate
5. stirringto stir for 15 min
6. filtrationThe resulting thick yellow-orange suspension was filtered
7. customto collect a yellow precipitate
8. customthe additional precipitate that formed
9. filtrationwas collected by filtration
10. customThe combined precipitates
11. customwere dried
12. customre-crystallized in EtOH (overnight in the dark)