反应详情

To a stirring solution of 2-methoxymethyloxy-4-isopropylbenzoic acid (3.0 g, 13.4 mmol) in THF (50 mL) was added sodium ethoxide (0.91 g, 13.4 mmol). After 15 min, the solvent was removed in vacuo and the residue was suspended in dichloromethane (50 mL). To this mixture was added a couple drops of DMF followed by oxalyl chloride (1.7 g, 13.4 mmol). After another 30 min, the solvent was removed in vacuo and the residue was again suspended in dichloromethane (150 mL). To this mixture was added pyridine (2.9 g, 36.5 mmol), followed by N-(5-chloropyridin-2-yl)-2-aminobenzamide (3.02 g, 12.2 mmol). After stirring for 2 h, the solvent was removed in vacuo and the residue was partitioned between ethyl acetate (400 mL) and water (200 mL). The organic phase was washed twice with 1 M citric acid, once with brine, twice with saturated aq sodium bicarbonate and once with brine. The organic phase was then dried with MgSO4 and filtered. To this solution was added silica gel (about 10 g) and the solvent was removed in vacuo. The resulting dry pack was loaded onto the top of a silica gel column loaded with 10% ethyl acetate in hexanes and eluted with a gradient of 10% ethyl acetate in hexanes through 30% ethyl acetate in hexanes. The clean product containing fractions were combined and concentrated in vacuo to give 2.18 g (39%) of off white solid. Another set of fractions which contained a small amount of impurity were combined and concentrated in vacuo to give 2.09 g (about 38%) of an off white solid.

1. customthe solvent was removed in vacuo
2. additionTo this mixture was added a couple drops of DMF
3. waitAfter another 30 min
4. customthe solvent was removed in vacuo
5. customthe solvent was removed in vacuo
6. customthe residue was partitioned between ethyl acetate (400 mL) and water (200 mL)
7. washThe organic phase was washed twice with 1 M citric acid, once with brine, twice with saturated aq sodium bicarbonate and once with brine
8. dry with materialThe organic phase was then dried with MgSO4
9. filtrationfiltered
10. additionTo this solution was added silica gel (about 10 g)
11. customthe solvent was removed in vacuo
12. customThe resulting dry pack
13. washeluted with a gradient of 10% ethyl acetate in hexanes through 30% ethyl acetate in hexanes
14. additionThe clean product containing fractions
15. concentrationconcentrated in vacuo
16. customto give 2.18 g (39%) of off white solid
17. concentrationconcentrated in vacuo
18. customto give 2.09 g (about 38%) of an off white solid