反应详情

4-Amino-2,3-difluoro-5-nitro-benzoic acid methyl ester 4 (12.0 g, 51.7 mmol) is suspended in xylenes (60 mL) and ortho-toluidine is added (55.2 mL, 517 mmol). The reaction mixture is heated to reflux with stirring under a nitrogen atmosphere. After 36 hours, the reaction mixture is cooled to room temperature, diluted with diethyl ether and washed with 10% aqueous HCl solution. The aqueous washings are extracted with diethyl ether. The combined organic extracts are concentrated under reduced pressure. The residue is dissolved in methylene chloride and filtered through silica gel in a fritted funnel, rinsing with methylene chloride. Three fractions are recovered. The first (2 liter) is nearly clean by HPLC. The second (1 liter) and third (1 liter) fractions are only partially pure. The first fraction is concentrated under reduced pressure and triturated with diethyl ether to give 11.2 g (68%) of clean desired product as a bright yellow solid: MS APCI (−) m/z 318 (M−1) detected.

1. temperatureThe reaction mixture is heated
2. temperatureto reflux
3. washwashed with 10% aqueous HCl solution
4. extractionThe aqueous washings are extracted with diethyl ether
5. concentrationThe combined organic extracts are concentrated under reduced pressure
6. dissolutionThe residue is dissolved in methylene chloride
7. filtrationfiltered through silica gel in a fritted funnel
8. washrinsing with methylene chloride
9. customThree fractions are recovered
10. concentrationThe first fraction is concentrated under reduced pressure
11. customtriturated with diethyl ether