反应 #2487448

反应方程式

4-chloro-2-(4-chloro-phenyl)-7-trifluoromethylquinazoline

ethylamine

→

precipitate

[2-(4-Chloro-phenyl)-7-trifluoromethyl-quinazolin-4-yl]ethylamine

溶剂

THF

THF

反应条件

后处理

1. 1
   其他The ice-bath was then removed
2. 2
   浓缩The reaction mixture was concentrated under reduced pressure
3. 3
   其他then partitioned between ethyl acetate (400 mL) and water (400 mL)
4. 4
   其他removing any undissolved solid
5. 5
   过滤by vacuum filtration
6. 6
   浓缩The filtrate was concentrated to approximately 200 mL
7. 7
   其他the resultant precipitate was removed by vacuum filtration
8. 8
   浓缩The filtrate was again concentrated to approximately 100 mL volume
9. 9
   其他the resultant precipitate was removed by vacuum filtration
10. 10
    温度Finally the filtrate was cooled to 0° C. upon which [2-(4-chloro-phenyl)-7-trifluoromethyl-quinazolin-4-yl]ethylamine
11. 11
    其他precipitated from solution

实验过程

To a stirred solution of 4-chloro-2-(4-chloro-phenyl)-7-trifluoromethylquinazoline (52.0 g, 0.15 mol) in THF (400 mL) at 0° C. was added dropwise a solution of ethylamine (0.45 mol, 230 mL, 2 M in THF. The ice-bath was then removed and the reaction mixture was allowed to stir at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure then partitioned between ethyl acetate (400 mL) and water (400 mL) removing any undissolved solid by vacuum filtration. The filtrate was concentrated to approximately 200 mL and the resultant precipitate was removed by vacuum filtration. The filtrate was again concentrated to approximately 100 mL volume and the resultant precipitate was removed by vacuum filtration. Finally the filtrate was cooled to 0° C. upon which [2-(4-chloro-phenyl)-7-trifluoromethyl-quinazolin-4-yl]ethylamine precipitated from solution. The precipitate (30 g) was isolated by vacuum filtration and dried under vacuum (10 mbar, 50° C.). A second amount of the precipitate of equal purity (19.6 g) was obtained following concentration of the filtrate to approximately 50 mL volume, cooling to 0° C., filtration and drying under vacuum. Combined yield=49.6 g, 93%; LC-MS: 2.9 min, 352 (M+); 1H NMR (DMSO-d6): δ 1.38 (t, 1 H, J=7 Hz), 3.77-3.85 (m, 2 H), 7.46 (d, 2 H, J=8.7 Hz), 7.64 (dd, 1 H, J=8.3, 1.8 Hz), 7.72-7.78 (br s, 1 H), 8.09 (s, 1 H), 8.17 (d, 1 H, J=8.3 Hz), 8.59 (d, 2 H, J=8.7 Hz).

来源