反应详情

2-(Methyloxy)-5-[(methyloxy)carbonyl]benzoic acid (1.96 g, 9.33 mmol) was suspended in 60 mL of DCM with stirring. DMF (0.036 mL, 0.46 mmol) was added via syringe. Oxalyl chloride (7.0 mL, 2.0M in dichloromethane, 14 mmol) was added dropwise via addition funnel. The addition funnel was rinsed with 10 mL of DCM. The reaction was stirred for 2 hours and concentrated in vacuo. The resultant solid was further dried under high vacuum pressure. The solid was dissolved in 60 mL of DCM with stirring. Pyridine (3.8 mL, 47 mmol), (4-dimethylamino)pyridine (0.0570 g, 0.467 mmol), and 2,6-difluoroaniline (3.0 mL, 28 mmol) were added to the solution. The reaction was stirred for 18 hours and poured into 1N HCl. The layers were separated, and the aqueous layer was washed once with DCM and once with diethyl ether. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography. The clean fractions (by TLC) were concentrated in vacuo to afford 1.56 g (52%) of the desired product. 1H NMR (400 MHz, DMSO-d6): δ 9.81 (s, 1H), 8.31 (d, J=2.0 Hz, 1H), 8.10 (dd, J=8.8, 2.0 Hz, 1H), 7.38 (m, 1H), 7.31 (d, J=88 Hz, 1H), 7.22-7.13 (m, 2H), 3.97 (s, 3H), 3.82 (s, 3H).

1. washThe addition funnel was rinsed with 10 mL of DCM
2. stirringThe reaction was stirred for 2 hours
3. concentrationconcentrated in vacuo
4. customThe resultant solid was further dried under high vacuum pressure
5. dissolutionThe solid was dissolved in 60 mL of DCM
6. stirringwith stirring
7. stirringThe reaction was stirred for 18 hours
8. customThe layers were separated
9. washthe aqueous layer was washed once with DCM and once with diethyl ether
10. dry with materialThe combined organic layers were dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe crude product was purified by flash chromatography
14. concentrationThe clean fractions (by TLC) were concentrated in vacuo