Reacción #607447

Ecuación de reacción

DIAD

3-bromo-6-methyl-5-nitro-pyridin-2-ol

2,2,2-trifluoro-1-[4-(trifluoromethyl)phenyl]ethanol

triphenylphosphine

→

title compound

Rendimiento 41.0%

5-Bromo-2-methyl-3-nitro-6-[2,2,2-trifluoro-1-[4-(trifluoromethyl)phenyl]ethoxy]pyridine

Rendimiento 41.0%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwere added at room temperature under inert atmosphere (Ar)
2. 2
   Otrothe temperature below 40° C
3. 3
   Otrowas consumed
4. 4
   Otroto reach room temperature
5. 5
   Otrobefore quenching with water (10 mL)
6. 6
   ExtracciónThe water phase was extracted with ethyl acetate (2×50 mL)
7. 7
   LavadoThe organic layer was washed with brine (20 mL)
8. 8
   Secadodried over anhydrous Na2SO4
9. 9
   Filtraciónfiltered
10. 10
    OtroThe solvent was removed in vacuo
11. 11
    Otroto give a brown residue, which
12. 12
    Otrowas purified by combiflash column chromatography (silica gel, heptane/ethyl acetate, v/v=95/5)
13. 13
    workup.ADDITIONFractions containing the pure compound
14. 14
    Otrowere collected
15. 15
    Concentraciónconcentrated in vacuo

Procedimiento

To a stirring suspension of 3-bromo-6-methyl-5-nitro-pyridin-2-ol (0.25 g, 1.07 mmol) in THF (7 mL), 2,2,2-trifluoro-1-[4-(trifluoromethyl)phenyl]ethanol (0.39 g, 1.61 mmol, 1.5 equiv) and triphenylphosphine (0.42 g, 1.61 mmol, 1.5 eq) were added at room temperature under inert atmosphere (Ar). To this mixture, DIAD (diisopropyl diazodicarboxylate) (0.33 mL, 1.61 mmol, 1.5 eq) was added dropwise over 10 minutes while keeping the temperature below 40° C. The reaction mixture was stirred for 6 h under heating at 60° C. After this time, TLC indicted that the starting material was consumed and the reaction mixture was allowed to reach room temperature before quenching with water (10 mL). The water phase was extracted with ethyl acetate (2×50 mL). The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4 and filtered. The solvent was removed in vacuo to give a brown residue, which was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate, v/v=95/5). Fractions containing the pure compound were collected and concentrated in vacuo to give the title compound (0.18 g, 41% yield) as a yellow oil.

Fuente