反应详情

3-Acetoxy-4-methoxybenzoic acid (5.0 g) was dissolved in the mixture of acetone (95 ml) and water (5 ml). To this solution were added ethyl chlorocarbonate (3.4 g) and triethylamine (2.9 g) under ice-cooling, and the mixture stirred for 0.5 hour. To this mixture was further added a solution of sodium azide (2.3 g) in water (10 ml), and the resulting mixture was further stirred at 0° for 1 hour, poured into ice-water, and extracted with ether. The extract was washed with saturated saline and dried over sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude acyl azide. The product, without purification, was dissolved in toluene (50 ml), and the solution was heated under reflux for 1 hour. The solvent was distilled off under reduced pressure. The crude isocyanate was dissolved in methanol (100 ml), and the mixture was heated under reflux for 1 hour. After the mixture was left to cool to room temperature, potassium carbonate (5.0 g) was added. The mixture was stirred at room temperature for 1 hour, and then water was added to the mixture. It was acidified with 10% hydrochloric acid and extraction with chloroform was conducted. The extract was washed with saturated saline and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (Wako Gel C-200, 100 g). Elution with chloroform gave N-methoxycarbonyl-3-hydroxy-4-methoxyaniline (4.1 g).

1. temperaturecooling
2. stirringthe resulting mixture was further stirred at 0° for 1 hour
3. extractionextracted with ether
4. washThe extract was washed with saturated saline
5. dry with materialdried over sodium sulfate
6. distillationthe solvent was distilled off under reduced pressure
7. customto obtain a crude acyl azide
8. customThe product, without purification
9. dissolutionwas dissolved in toluene (50 ml)
10. temperaturethe solution was heated
11. temperatureunder reflux for 1 hour
12. distillationThe solvent was distilled off under reduced pressure
13. dissolutionThe crude isocyanate was dissolved in methanol (100 ml)
14. temperaturethe mixture was heated
15. temperatureunder reflux for 1 hour
16. waitAfter the mixture was left
17. additionpotassium carbonate (5.0 g) was added
18. stirringThe mixture was stirred at room temperature for 1 hour
19. additionwater was added to the mixture
20. extractionIt was acidified with 10% hydrochloric acid and extraction with chloroform
21. washThe extract was washed with saturated saline
22. dry with materialdried over sodium sulfate
23. distillationthe solvent was distilled off under reduced pressure
24. customThe residue thus obtained
25. customwas purified by silica gel column chromatography (Wako Gel C-200, 100 g)
26. washElution with chloroform