反应详情

温度

90 °C

Methyl 2-iodo-6-methylbenzoate (I58) (2.00 g, 7.245 mmol) and NBS (1.418 g, 7.969 mmol) were stirred in chlorobenzene (50 mL) and benzoyl peroxide (75% w/w, 0.234 g, 0.724 mmol) was added. The reaction was stirred at 90° C. for 18 hours, cooled to room temperature, filtered and the precipitate was washed with cyclohexane (4×10 mL). The combined filtrates were evaporated, and the resulting brown oil was diluted with THF (50 mL). Aqueous ammonia solution (20 mL) was added, and the mixture was stirred vigorously for 17 hours. The mixture was diluted with water (20 mL) and the THF was removed in vacuo. DCM (150 mL) was added, the layers were separated and the aqueous layer was extracted with DCM (2×100 mL), the combined organics were washed with brine (100 mL), dried (MgSO4) and filtered. Silica gel was added and the volatiles were removed in vacuo to give the crude material absorbed onto silica gel. The material was purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., then 0-20% methanol in EtOAc) to give the title compound (I59) (0.757 g, 40% yield) as a beige solid; 1H NMR (400 MHz, CDCl3) δ 7.93 (dd, J=7.8, 0.7 Hz, 1H), 7.46 (dd, J=7.5, 0.8 Hz, 1H), 7.26-7.21 (m, 1H), 7.10 (brs, 1H), 4.37 (d, J=0.6 Hz, 2H). LCMS Method C: rt 5.06 min; m/z 260.0 [M+H]+.

1. temperaturecooled to room temperature
2. filtrationfiltered
3. washthe precipitate was washed with cyclohexane (4×10 mL)
4. customThe combined filtrates were evaporated
5. additionthe resulting brown oil was diluted with THF (50 mL)
6. additionAqueous ammonia solution (20 mL) was added
7. stirringthe mixture was stirred vigorously for 17 hours
8. additionThe mixture was diluted with water (20 mL)
9. customthe THF was removed in vacuo
10. additionDCM (150 mL) was added
11. customthe layers were separated
12. extractionthe aqueous layer was extracted with DCM (2×100 mL)
13. washthe combined organics were washed with brine (100 mL)
14. dry with materialdried (MgSO4)
15. filtrationfiltered
16. additionSilica gel was added
17. customthe volatiles were removed in vacuo
18. customto give the crude material
19. customabsorbed onto silica gel
20. customThe material was purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.