Reaktion #1153160

Reaktionsgleichung

chlorofluoromethane

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

potassium carbonate

sodium bromide

→

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

Lösungsmittel

DMF

DMF

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 500 mL nitrogen purged round bottom flask fitted with a dry-ice condenser
2. 2
   Sonstigecondensed
3. 3
   Sonstigethe dry-ice bath was removed
4. 4
   TemperaturThe pale yellow suspension was warmed first to room temperature
5. 5
   Sonstigeto 70-75° C.
6. 6
   TemperaturGentle 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
   Temperaturto warm to room temperature overnight
10. 10
    SonstigeThe white suspension which resulted
11. 11
    Extraktionextracted with ether (1×1 L, 2×500 mL)
12. 12
    WaschenThe combined extracts were washed with water (4×250 mL) and brine (500 mL)
13. 13
    Trocknendried with magnesium sulfate
14. 14
    Filtrationfiltered
15. 15
    Einengenthe filtrate concentrated
16. 16
    EinengenDuring concentration the product
17. 17
    Sonstigeto crystallize
18. 18
    EinengenThe filtrare was concentrated to a small volume
19. 19
    Sonstigethe mixture flushed with hexanes
20. 20
    TemperaturThe resulting slurry was cooled to 0° C., aged 1 hr
21. 21
    Filtrationfiltered
22. 22
    Waschenthe cake washed with hexanes
23. 23
    SonstigeThe yield
24. 24
    Sonstigeupon drying

Vorschrift

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.

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