反应详情

4-Chloro-2-pyridinecarboxamide (93.9 g, 0.6 moles) and TEA (125 mL, 0.9 moles) in EtOAc (500 mL) was cooled to 0.2° C. via an external chiller unit. TFAA (92 mL, 0.66 moles) was added via addition funnel over 40 min. The internal temperature rose to 10° C. during the addition. The temperature at the completion of the addition was 0.0° C. After addition, the chiller was turned off. After an additional 30 min, HPLC analysis showed 4.3% (LCAP) of the starting material. An additional 8.3 mL (0.06 moles) of TFAA was added. After stirring the reaction mixture for an additional 20 min, HPLC analysis indicated complete conversion. 10% Aqueous K2CO3 (w/v, 500 mL) was added. The internal temperature rose from 13.7 to 22.0° C. The mixture was transferred to a separatory funnel after stirring for 20 min. The layers were separated and the aqueous layer extracted with EtOAc (150 mL). The combined organic layers were washed with 10% aqueous citric acid (w/v, 300 mL), dried (Na2SO4), filtered, and concentrated. The crude product was dried in a vacuum oven at 50° C. for 16 h to afford 72.85 g (87%) of the title compound: 1H NMR (400 MHz, CDCl3) δ 8.6 (m, 1 H), 7.7 (m, 1 H), 7.5 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 151.8, 145.3, 134.9, 128.7, 127.4, 116.1; HPLC>99% (LCAP).

1. additionThe internal temperature rose to 10° C. during the addition
2. additionThe temperature at the completion of the addition
3. customwas 0.0° C
4. additionAfter addition
5. customrose from 13.7 to 22.0° C
6. customThe mixture was transferred to a separatory funnel
7. stirringafter stirring for 20 min
8. customThe layers were separated
9. extractionthe aqueous layer extracted with EtOAc (150 mL)
10. washThe combined organic layers were washed with 10% aqueous citric acid (w/v, 300 mL)
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated
14. dry with materialThe crude product was dried in a vacuum oven at 50° C. for 16 h