1,2-Dichloroethane → 2-bromo-7-iodo-3-(trifluoromethoxy)-9H-xanthen-9-one

온도

2.5 °C

In a 500 mL flask, 2-fluoro-5-iodobenzoyl chloride (6.06 g, 21.3 mmol) and 1-bromo-4-methoxy-2-(trifluoromethoxy)benzene (5.77 g, 21.3 mmol) were dissolved in 1,2-dichloroethane (50.7 mL, 21.3 mmol) and the solution was cooled to 0 to 5° C. Aluminum chloride (2.84 g, 21.3 mmol) was added portionwise to the solution. The red solution was warmed to rt. After 2 h, LCMS showed mainly (5-bromo-2-methoxy-4-(trifluoromethoxy)phenyl)(2-fluoro-5-iodophenyl)methanone. The whole was refluxed for 1 h. LCMS showed complete consumption of (5-bromo-2-methoxy-4-(trifluoromethoxy)phenyl)(2-fluoro-5-iodophenyl)methanone. The reaction was cooled to rt. Ice (5-10 chips) and concentrated HCl (2 mL) was added until pH ˜1. The whole was stirred at rt for 30 min. The resulting slurry was extracted with ether (3×80 mL). The organic layer was washed with water, dried over MgSO4, filtered, and concentrated to afford a semi-black solid that was carried on to the next step. The crude was added to a mixture of ethanol (85 mL, 21.3 mmol), methanol (30.4 mL, 21.3 mmol), and sodium methoxide (2.30 g, 42.6 mmol) at rt. After refluxing for 1 h, LCMS showed mainly the cyclized xanthenone product. The whole was cooled to rt and concentrated. Water (80 mL) and EtOAc (120 mL) was added. The product was extracted with EtOAc (2×80 mL). The organic layer was separated, combined, dried over MgSO4, filtered, and concentrated. Trituration with hexanes gave 2-bromo-7-iodo-3-(trifluoromethoxy)-9H-xanthen-9-one (2.94 g, 6.06 mmol, 29% yield) as a gray solid. LCMS (ESI) calcd for C14H5BrF3IO3: [M]+=484. Found [M+H]+=485.

1. temperatureThe red solution was warmed to rt
2. temperatureThe whole was refluxed for 1 h
3. customconsumption of (5-bromo-2-methoxy-4-(trifluoromethoxy)phenyl)(2-fluoro-5-iodophenyl)methanone
4. temperatureThe reaction was cooled to rt
5. additionIce (5-10 chips) and concentrated HCl (2 mL) was added until pH ˜1
6. extractionThe resulting slurry was extracted with ether (3×80 mL)
7. washThe organic layer was washed with water
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto afford a semi-black solid
12. temperatureAfter refluxing for 1 h
13. temperatureThe whole was cooled to rt
14. concentrationconcentrated
15. additionWater (80 mL) and EtOAc (120 mL) was added
16. extractionThe product was extracted with EtOAc (2×80 mL)
17. customThe organic layer was separated
18. dry with materialdried over MgSO4
19. filtrationfiltered
20. concentrationconcentrated

ORD 기록

ord-0ca9690638104c1e9d493f646d48983e

출처 데이터셋

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08883782B2