Reacción #1153160

Ecuación de reacción

chlorofluoromethane

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

potassium carbonate

sodium bromide

→

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

Disolventes

DMF

DMF

water

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroA 500 mL nitrogen purged round bottom flask fitted with a dry-ice condenser
2. 2
   Otrocondensed
3. 3
   Otrothe dry-ice bath was removed
4. 4
   TemperaturaThe pale yellow suspension was warmed first to room temperature
5. 5
   Otroto 70-75° C.
6. 6
   TemperaturaGentle 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
   Temperaturato warm to room temperature overnight
10. 10
    OtroThe white suspension which resulted
11. 11
    Extracciónextracted with ether (1×1 L, 2×500 mL)
12. 12
    LavadoThe combined extracts were washed with water (4×250 mL) and brine (500 mL)
13. 13
    Secadodried with magnesium sulfate
14. 14
    Filtraciónfiltered
15. 15
    Concentraciónthe filtrate concentrated
16. 16
    ConcentraciónDuring concentration the product
17. 17
    Otroto crystallize
18. 18
    ConcentraciónThe filtrare was concentrated to a small volume
19. 19
    Otrothe mixture flushed with hexanes
20. 20
    TemperaturaThe resulting slurry was cooled to 0° C., aged 1 hr
21. 21
    Filtraciónfiltered
22. 22
    Lavadothe cake washed with hexanes
23. 23
    OtroThe yield
24. 24
    Otroupon drying

Procedimiento

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.

Fuente