Réaction #607447

Équation de réaction

DIAD

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

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

triphenylphosphine

→

title compound

Rendement 41.0%

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

Rendement 41.0%

Solvants

THF

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONwere added at room temperature under inert atmosphere (Ar)
2. 2
   Autrethe temperature below 40° C
3. 3
   Autrewas consumed
4. 4
   Autreto reach room temperature
5. 5
   Autrebefore quenching with water (10 mL)
6. 6
   ExtractionThe water phase was extracted with ethyl acetate (2×50 mL)
7. 7
   LavageThe organic layer was washed with brine (20 mL)
8. 8
   Séchagedried over anhydrous Na2SO4
9. 9
   Filtrationfiltered
10. 10
    AutreThe solvent was removed in vacuo
11. 11
    Autreto give a brown residue, which
12. 12
    Autrewas purified by combiflash column chromatography (silica gel, heptane/ethyl acetate, v/v=95/5)
13. 13
    workup.ADDITIONFractions containing the pure compound
14. 14
    Autrewere collected
15. 15
    Concentrationconcentrated in vacuo

Mode opératoire

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.

Source