Реакция #607447

Уравнение реакции

DIAD

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

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

triphenylphosphine

→

title compound

Выход 41.0%

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

Выход 41.0%

Растворители

THF

Условия реакции

Обработка

1. 1
   workup.ADDITIONwere added at room temperature under inert atmosphere (Ar)
2. 2
   Другоеthe temperature below 40° C
3. 3
   Другоеwas consumed
4. 4
   Другоеto reach room temperature
5. 5
   Другоеbefore quenching with water (10 mL)
6. 6
   ЭкстракцияThe water phase was extracted with ethyl acetate (2×50 mL)
7. 7
   ПромывкаThe organic layer was washed with brine (20 mL)
8. 8
   Сушкаdried over anhydrous Na2SO4
9. 9
   Фильтрацияfiltered
10. 10
    ДругоеThe solvent was removed in vacuo
11. 11
    Другоеto give a brown residue, which
12. 12
    Другоеwas purified by combiflash column chromatography (silica gel, heptane/ethyl acetate, v/v=95/5)
13. 13
    workup.ADDITIONFractions containing the pure compound
14. 14
    Другоеwere collected
15. 15
    Концентрированиеconcentrated in vacuo

Методика

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.

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