Reaction #607445

Reaction equation

DIAD

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

2,2,2-trifluoro-1-(4-fluorophenyl)ethanol

triphenylphosphine

→

title compound

Yield 62.5%

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

Yield 62.5%

Solvents

THF

Conditions

Workup

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

Procedure

To a stirred suspension of 3-bromo-6-methyl-5-nitro-pyridin-2-ol (0.10 g, 0.43 mmol) in THF (3 mL), 2,2,2-trifluoro-1-(4-fluorophenyl)ethanol (0.13 g, 0.64 mmol, 1.5 equiv) and triphenylphosphine (0.17 g, 0.64 mmol, 1.5 eq) were added at room temperature under inert atmosphere (Ar). To this mixture, DIAD (diisopropyl diazodicarboxylate) (0.13 mL, 0.64 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 had been 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 (3×15 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 (0.11 g, 62% yield) as a yellow oil.

Source