反应详情

温度

0 °C

To ethyl isocyanate (1.65 ml, 1.48 g, 20.8 mM) in pyridine (9.2 ml) at 0° C. was added a cold solution of 2-amino-5,6-dimethoxybenzoic acid ethyl ester (3.0 g, 20.8 mM) in pyridine (16.7 ml). The solution was stirred at 0° C. for thirty minutes, then kept at room temperature for one hour. During this time, a precipitate formed. The mixture was concentrated to dryness to give an off-white solid. This was dissolved in 69.9 ml of 1N NaOH (4:1 MeOH-H2O) and heated at reflux for two hours. The solvent was removed in vacuo and the residue dissolved in H2O (150 ml). The mixture was taken to pH 6 with acetic acid and the resulting white solid filtered, washed with H2O (50 ml), and dried to give crude product as a white solid; 3.12 g; mp 208°-211° C. Recrystallization from isopropanol (100 ml) and drying afforded the title compound as a white solid; 2.09 g; mp 212°-214° C., total yield 80.5%, CF3COOH(TMS), 7.60 (d, 1H, J7,8 =9.0 Hz, 7-H), 7.13 (d, 1H, J8,7 =9.0 Hz, 8-H), 4.20 (9, 2H, J=6.0 Hz, 9-H), 4.19 (s, 3H, 5 or 6-OCH3), 4.05 (s, 3H, 5 or 6-OCH3), 1.40 (t, 3H, J=6.0 Hz, 10-H). M+ 250.

1. customDuring this time, a precipitate formed
2. concentrationThe mixture was concentrated to dryness
3. customto give an off-white solid
4. temperatureheated
5. temperatureat reflux for two hours
6. customThe solvent was removed in vacuo
7. dissolutionthe residue dissolved in H2O (150 ml)
8. filtrationthe resulting white solid filtered
9. washwashed with H2O (50 ml)
10. customdried
11. customto give crude product as a white solid
12. customRecrystallization from isopropanol (100 ml)
13. customdrying