반응 #1153160

반응 방정식

chlorofluoromethane

2-hydroxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzaldehyde

potassium carbonate

sodium bromide

→

2-Fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzaldehyde

용매

DMF

DMF

water

반응 조건

후처리

1. 1
   기타A 500 mL nitrogen purged round bottom flask fitted with a dry-ice condenser
2. 2
   기타condensed
3. 3
   기타the dry-ice bath was removed
4. 4
   온도The pale yellow suspension was warmed first to room temperature
5. 5
   기타to 70-75° C.
6. 6
   온도Gentle reflux
7. 7
   workup.ADDITIONan additional 30 g of NaBr was added
8. 8
   workup.WAITThe condenser was kept cold for ca. 10 h
9. 9
   온도to warm to room temperature overnight
10. 10
    기타The white suspension which resulted
11. 11
    추출extracted with ether (1×1 L, 2×500 mL)
12. 12
    세척The combined extracts were washed with water (4×250 mL) and brine (500 mL)
13. 13
    건조dried with magnesium sulfate
14. 14
    여과filtered
15. 15
    농축the filtrate concentrated
16. 16
    농축During concentration the product
17. 17
    기타to crystallize
18. 18
    농축The filtrare was concentrated to a small volume
19. 19
    기타the mixture flushed with hexanes
20. 20
    온도The resulting slurry was cooled to 0° C., aged 1 hr
21. 21
    여과filtered
22. 22
    세척the cake washed with hexanes
23. 23
    기타The yield
24. 24
    기타upon drying

실험 절차

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.

출처