反应详情

温度

3.5 °C

2-fluoro-4-iodo-pyridine-3-carbaldehyde (50 g, 199.2 mmol) was dissolved in dry THF (600.0 mL) and the mixture cooled to 3.5° C. Trimethyl-(trifluoromethyl)silane (102.0 g, 106.0 mL, 717.1 mmol) was added and the mixture was stirred for 10 minutes (temp held at 3.6° C.) then tetrabutylammonium fluoride (9.960 mL of 1 M, 9.960 mmol) (in THF) was added dropwise. The temperature increased rapidly to 23.6° C. on adding ca 0.5 ml. The remainder of the solution was added slowly over 10 minutes—the reaction temperature did not increase further. The reaction mixture became dark brown in colour and was diluted by slow addition of 6M HCl (500 ml) with the ice bath still in place. The temperature increased to a maximum of 27.8° C. The mixture was stirred for 10 minutes and then re-cooled in an ice bath and sodium hydroxide (120 g total) was added partially as solid, then as a concentrated solution in water. The pH of the final mixture was 6-7. The mixture was diluted with EtOAc (500 ml) and the organic layer removed. The aqueous was extracted with EtOAc (2×500 ml) and the combined organics washed with brine (250 ml), dried (MgSO4), filtered and concentrated to a dark brown oil which was purified by filtration through a silica plug eluting with a 15%-30% EtOAc/Hexanes solvent system. The product was collected as a beige solid (45 g, 71% Yield).

1. temperatureThe temperature increased rapidly to 23.6° C.
2. additionon adding ca 0.5 ml
3. additionThe remainder of the solution was added slowly over 10 minutes—the reaction temperature
4. temperaturedid not increase further
5. temperatureThe temperature increased to a maximum of 27.8° C
6. stirringThe mixture was stirred for 10 minutes
7. temperaturere-cooled in an ice bath
8. customthe organic layer removed
9. extractionThe aqueous was extracted with EtOAc (2×500 ml)
10. washthe combined organics washed with brine (250 ml)
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated to a dark brown oil which
14. filtrationwas purified by filtration through a silica plug
15. washeluting with a 15%-30% EtOAc/Hexanes solvent system