反応 #60241

反応方程式

4-Amino-2,3-difluoro-5-nitro-benzoic acid methyl ester

ortho-toluidine

→

clean desired product

収率 68.0%

4-Amino-3-fluoro-5-nitro-2-o-tolylamino-benzoic acid methyl ester

収率 68.0%

溶媒

diethyl ether

—

xylenes

反応条件

後処理

1. 1
   温度The reaction mixture is heated
2. 2
   温度to reflux
3. 3
   洗浄washed with 10% aqueous HCl solution
4. 4
   抽出The aqueous washings are extracted with diethyl ether
5. 5
   濃縮The combined organic extracts are concentrated under reduced pressure
6. 6
   workup.DISSOLUTIONThe residue is dissolved in methylene chloride
7. 7
   ろ過filtered through silica gel in a fritted funnel
8. 8
   洗浄rinsing with methylene chloride
9. 9
   その他Three fractions are recovered
10. 10
    濃縮The first fraction is concentrated under reduced pressure
11. 11
    その他triturated with diethyl ether

実験手順

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.

出典