반응 #640625

반응 방정식

2-(4-isopropylthiazol-2-yl)-4-hydroxy-7-methoxy-8-methyl-quinoline

Phosphorous oxychloride

NaOH

→

title compound

수율 91.0%

2-(4-isopropylthiazol-2-yl)-4-chloro-7-methoxy-8-methyl-quinoline

수율 91.0%

반응 조건

후처리

1. 1
   기타consumption of the starting material
2. 2
   workup.WAITThe reaction mixture was left
3. 3
   온도to cool to ambient temperature
4. 4
   기타the solvent removed under vacuum
5. 5
   workup.ADDITIONThe residue was diluted with ethyl acetate (80 mL)
6. 6
   온도the reaction mixture cooled to 0° C
7. 7
   workup.ADDITION2M aqueous sodium hydroxide solution was added portion wise until the pH of the aqueous phase
8. 8
   workup.STIRRINGstir
9. 9
   기타reaction mixture for 1 min
10. 10
    기타The two layers were separated
11. 11
    세척the organic layer was further washed with water (50 mL) and brine (50 mL)
12. 12
    건조The organic layer was dried over sodium sulphate
13. 13
    여과filtered
14. 14
    기타the solvent removed under vacuum

실험 절차

2-(4-isopropylthiazol-2-yl)-4-hydroxy-7-methoxy-8-methyl-quinoline (4.63 g, 13.6 mmol., 1.0 eq.) was charged into a 100 mL round bottom flask. Phosphorous oxychloride (45 mL) was added and the reaction mixture stirred at 90° C. for 3 hours. Monitoring the reaction mixture by 1H NMR showed full consumption of the starting material. The reaction mixture was left to cool to ambient temperature and the solvent removed under vacuum. The residue was diluted with ethyl acetate (80 mL) and the reaction mixture cooled to 0° C. 2M aqueous sodium hydroxide solution was added portion wise until the pH of the aqueous phase was 14 (stir reaction mixture for 1 min between every NaOH addition). The two layers were separated and the organic layer was further washed with water (50 mL) and brine (50 mL). The organic layer was dried over sodium sulphate, filtered and the solvent removed under vacuum to give 4.11 g (91%) of the title compound as a pale brown solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.28 (s, 1 H), 8.09 (d, J=9.16 Hz, 1 H), 7.38 (d, J=9.16 Hz, 1 H), 7.06 (s, 1 H), 4.02 (s, 3 H), 3.20 (spt, J=6.87 Hz, 1 H), 2.73 (s, 3 H), 1.40 (d, J=6.87 Hz, 6 H).

출처