反应详情

To a -78° C. solution of 18 (890 mg, 3.0 mmol) in dry THF (20 ml) was slowly added MeLi/LiBr (1.5M in ether, 2.2 ml, 3.3 mmol). The solution was stirred 30 min. at -78° C. at which time Br2 (excess) was added dropwise. The solution was warmed to room temperature, quenched with water, and the mixture extracted with ether. The combined ether extracts were dried (MgSO4) and concentrated. The residue was taken up in CH2Cl2 and passed through a short silica gel pad. The appropriate fractions were concentrated to afford a material which was immediately diluted with CHCl3 (20 ml). To this solution was added excess CH3CO2OH (32% solution in dilute HOAc) and the mixture was stirred overnight. The mixture was then poured into saturated NaHCO3 (aq) and extracted with ether. The combined ether extracts were dried (MgSO4) and concentrated to a tan solid to which was added excess POCl3 at 0° C. The mixture was warmed to 60° C., stirred for 15 min., and then cooled to room temperature. 1M NaOH was added and the mixture was extracted with ether. The combined ether extracts were dried (MgSO4) and concentrated to a residue which was purified by HPLC (Whatman Partisil 10 column, 90:10 CHCl3 :EtOAc) to afford 7-Bromo-2-chloroquinoline 19 (70 mg, 10% from 18). 1H NMR d (ppm): 7.4 d (CH arom), 7.7 s (2 CH arom), 8.2 d (CH arom), 8.3 s (CH arom).

1. customTo a -78° C.
2. additionwas added dropwise
3. customquenched with water
4. extractionthe mixture extracted with ether
5. dry with materialThe combined ether extracts were dried (MgSO4)
6. concentrationconcentrated
7. concentrationThe appropriate fractions were concentrated
8. customto afford a material which
9. extractionextracted with ether
10. dry with materialThe combined ether extracts were dried (MgSO4)
11. concentrationconcentrated to a tan solid to which
12. additionwas added excess POCl3 at 0° C
13. temperatureThe mixture was warmed to 60° C.
14. stirringstirred for 15 min.
15. temperaturecooled to room temperature
16. addition1M NaOH was added
17. extractionthe mixture was extracted with ether
18. dry with materialThe combined ether extracts were dried (MgSO4)
19. concentrationconcentrated to a residue which
20. customwas purified by HPLC (Whatman Partisil 10 column, 90:10 CHCl3 :EtOAc)