반응 #2487448

반응 방정식

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

ethylamine

→

precipitate

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

용매

THF

THF

반응 조건

후처리

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

실험 절차

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).

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