反应详情

温度

0 °C

In a round bottom flask containing concentrated sulfuric acid (10 mL) was added ice-cold water (10 mL) while maintaining the temperature around 0° C. Sodium nitrite (3.7 g, 53 mmol) was added portion wise followed by the drop wise addition of hypophosphorous acid (8 mL). This was followed by drop wise addition of a solution of dimethyl 2-amino-3,5-dichlorobenzene-1,4-dicarboxylate (5 g, 17.9 mmol, Step a) in acetic acid (10 mL). The resulting reaction mixture was stirred at 0° C. for 2 hours and then stored in a refrigerator at −10° C. for 15 hours. The reaction mixture was stirred at room temperature for additional 2 hours. The reaction mixture was again cooled to 0° C. and neutralized with aqueous ammonia solution, partitioned with ethyl acetate (2×15 mL). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography using ethyl acetate in hexane (4%) to yield dimethyl 2,6-dichlorobenzene-1,4-dicarboxylate as a pale yellow crystalline solid (3.8 g, 79%).

1. customThe resulting reaction mixture
2. waitstored in a refrigerator at −10° C. for 15 hours
3. stirringThe reaction mixture was stirred at room temperature for additional 2 hours
4. custompartitioned with ethyl acetate (2×15 mL)
5. washThe combined organic layer was washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by silica gel column chromatography