反应详情

温度

-78 °C

A 500 mL nitrogen purged round bottom flask fitted with a dry-ice condenser was cooled to −78° C. and 50 mL (ca. 40 g by cylinder difference) of chlorofluoromethane was condensed. DMF (200 mL), 2-hydroxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzaldehyde (40 g, 0.155 mol), powdered potassium carbonate (22 g, 0.159 mol, 1.03 equiv) and sodium bromide (22 g, 0.21 mol) were carefully added. An additional 100 mL of DMF was added and the dry-ice bath was removed. The pale yellow suspension was warmed first to room temperature, then to 70-75° C. (oil bath). Gentle reflux was noted. After 3 h, an additional 30 g of NaBr was added. The condenser was kept cold for ca. 10 h and allowed to warm to room temperature overnight. The white suspension which resulted was diluted with 2 L of water and extracted with ether (1×1 L, 2×500 mL). The combined extracts were washed with water (4×250 mL) and brine (500 mL), dried with magnesium sulfate, filtered and the filtrate concentrated. During concentration the product began to crystallize. The filtrare was concentrated to a small volume and the mixture flushed with hexanes. The resulting slurry was cooled to 0° C., aged 1 hr, filtered, and the cake washed with hexanes. The yield upon drying was 42.2 g (93.8%) of white crystalline 2-fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzaldehyde: 1H NMR (CDCI3) δ 5.91 (d, JH-F=30.5 Hz, 2H), 7.47 (d, J=9 Hz, 1H), 7.72 (dd, J=9, 2.7 Hz, 1H), 8.02 (d, J=2.7 Hz, 1H), 10.49 (s, 1H). MS (EI) m/z 290. Anal. Calcd for C10H6F4N4O2: C, 41.39; H, 2.08; F, 26.19; N, 19.31. Found: C, 41.39; H, 1.98; F, 25.79; N, 19.53.

1. customA 500 mL nitrogen purged round bottom flask fitted with a dry-ice condenser
2. customcondensed
3. customthe dry-ice bath was removed
4. temperatureThe pale yellow suspension was warmed first to room temperature
5. customto 70-75° C.
6. temperatureGentle reflux
7. additionan additional 30 g of NaBr was added
8. waitThe condenser was kept cold for ca. 10 h
9. temperatureto warm to room temperature overnight
10. customThe white suspension which resulted
11. extractionextracted with ether (1×1 L, 2×500 mL)
12. washThe combined extracts were washed with water (4×250 mL) and brine (500 mL)
13. dry with materialdried with magnesium sulfate
14. filtrationfiltered
15. concentrationthe filtrate concentrated
16. concentrationDuring concentration the product
17. customto crystallize
18. concentrationThe filtrare was concentrated to a small volume
19. customthe mixture flushed with hexanes
20. temperatureThe resulting slurry was cooled to 0° C., aged 1 hr
21. filtrationfiltered
22. washthe cake washed with hexanes
23. customThe yield
24. customupon drying