反应详情

温度

11 °C

A suspension of NaH (60%, 8.0 g, 0.2 mole) in dry THF (40 ml) was prepared, and a mixture of diethyl malonate (32.0 g, 0.2 mole) and THF (50 ml) was slowly added into the suspension to provide a mixture. The mixture was cooled to 10 to 12° C., and a solution of ClCH2COCl (11.3 g, 0.1 mole) in THF (100 ml) was added dropwise thereinto. Then, the reaction solution was kept at 10 to 12° C. for 1 hour, warmed by warm water (40 to 45° C.) for about 1 hour, and then cooled to 10 to 12° C. A solution of the ethyl 2-(2′-aminophenyl)acetate (0.1 mole) prepared in step (a) in THF (50 ml) was added dropwise into the above reaction solution, and then stirred at room temperature for 1 hour and heated on a water bath for several hours. The obtained reaction solution was examined by TLC to determine whether the reaction was complete. Then, the reaction solution was vacuum concentrated to remove most of the THF. Ice water (600 ml) was poured into the vacuum concentration flask. Then, the reaction solution in the vacuum concentration flask was extracted by CHCl3 several times. The obtained extract was washed by water and dried by dry MgSO4, and vacuum concentrated to remove CHCl3. The concentrated liquid was placed at room temperature for crystallization. The crystal was collected and recrystallized by ethanol to obtain 13.66 g of a white acicular crystal. The productivity was 41% and the melting point of the crystal was 91.2° C. The data of the optical spectrum was as follows: MS (m/z, %): 332.8 (M+, 35.85), 333.8 (M++1, 7.73); IR (KBr disc) cm−1: 3121.86 (—NH—), 1737.28 (C8′═O), 1698.3 (C4=O), 1664.19 (C3-CO-OEt); UVλmax nm (MeOH) (log ε): 291.0 (3.825); 1H-NMR (200 MHz, DMSO-d6) δ: 1.176 (3H, t, J=7 Hz, H-10′), 1.23 (3H, t, 166J=7 Hz, H-2″), 3.763 (2H, s, H-7′), 4.049 (2H, q, J=7 Hz, H-9′), 4.192 (2H, q, J=7 Hz, H-2″), 4.573 (2H, s, H-5), 7.321˜7.453 (4H, m, H-3′, H-4′, H-5′, H-6′), 10.115 (1H, s, NH); 13C-NMR (200 MHz, DMSO-d6) δ: 14.09 (C-10′), 14.65 (C-2″), 37.29 (C-7′), 56.30 (C-1″), 60.96 (C-9′), 75.17 (C-5′), 86.93 (C-3), 126.79 (C-6′), 127.64 (C-4′), 128.17 (C-2′), 130.33 (C-3′), 131.44 (C-5′), 134.03 (C-1′), 164.09 (C-2), 170.88 (C-8′), 177.90 (C-3″), 188.98 (C-4).

1. customwas prepared
2. additionwas slowly added into the suspension
3. customto provide a mixture
4. temperaturewarmed
5. temperaturecooled to 10 to 12° C
6. temperatureheated on a water bath for several hours
7. customThe obtained reaction solution
8. concentrationconcentrated
9. customto remove most of the THF
10. additionIce water (600 ml) was poured into the vacuum concentration flask
11. concentrationThen, the reaction solution in the vacuum concentration flask
12. extractionwas extracted by CHCl3 several times
13. extractionThe obtained extract
14. washwas washed by water
15. dry with materialdried by dry MgSO4, and vacuum
16. concentrationconcentrated
17. customto remove CHCl3
18. customThe concentrated liquid was placed at room temperature for crystallization
19. customThe crystal was collected
20. customrecrystallized by ethanol
21. customto obtain 13.66 g of a white acicular crystal
22. customwas 91.2° C