反应 #607447

反应方程式

DIAD

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

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

triphenylphosphine

→

title compound

收率 41.0%

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

收率 41.0%

溶剂

THF

反应条件

后处理

1. 1
   workup.ADDITIONwere added at room temperature under inert atmosphere (Ar)
2. 2
   其他the temperature below 40° C
3. 3
   其他was consumed
4. 4
   其他to reach room temperature
5. 5
   其他before quenching with water (10 mL)
6. 6
   萃取The water phase was extracted with ethyl acetate (2×50 mL)
7. 7
   洗涤The organic layer was washed with brine (20 mL)
8. 8
   干燥dried over anhydrous Na2SO4
9. 9
   过滤filtered
10. 10
    其他The solvent was removed in vacuo
11. 11
    其他to give a brown residue, which
12. 12
    其他was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate, v/v=95/5)
13. 13
    workup.ADDITIONFractions containing the pure compound
14. 14
    其他were collected
15. 15
    浓缩concentrated in vacuo

实验过程

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.

来源