反应详情

A 250 mL round bottom flask was charged with tert-butyl (4-chloro-3-iodopyridin-2-yl)carbamate (4.5 g, 12.69 mmol) and dissolved in DCE (50.8 mL). To that stirring solution was added anisole (2.77 mL, 25.4 mmol) followed by TFA (14.67 mL, 190 mmol) at rt. After 1.5 hours, LCMS showed clean and complete consumption of the starting material to a large peak with the desired mass (m/z=254 [M+H]+Methanol/Water/TFA Phenomenex Luna C18, 30×2 mm, 3u ES+/−). The mixture was concentrated under reduced pressure into a collection bulb that was pretreated with 3.0 M NaOH. The crude mixture was then redissolved in toluene to aid in the removal of any volatiles. The crude solid was then diluted with EtOAc and sat'd sodium bicarbonate. The mixture was stirred for 15 min. The contents of the flask were transferred into a separatory funnel where the aqueous layer was extracted twice with EtOAc and discarded. The combined organics were washed with brine, dried with magnesium sulfate, and concentrated under reduced pressure. The crude material was dissolved in a small amount of ethanol and then heated with a heat gun. The mixture was let sit and then after 5 min cooled in an acetone dry ice bath. The solids were sonicated and collected by filtration. The mother liquor was concentrated and the above procedure was repeated. 4-chloro-3-iodopyridin-2-amine (2.1 g, 65% yield) was collected as a solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.88 (d, J=5.3 Hz, 1H), 6.74 (d, J=5.3 Hz, 1H), 5.20 (br. s., 2H).

1. customcomplete consumption of the starting material to a large peak with the desired mass (m/z=254 [M+H]+Methanol/Water/TFA Phenomenex Luna C18, 30×2 mm, 3u ES+/−)
2. concentrationThe mixture was concentrated under reduced pressure into a collection bulb that
3. dissolutionThe crude mixture was then redissolved in toluene
4. customto aid in the removal of any volatiles
5. additionThe crude solid was then diluted with EtOAc
6. customThe contents of the flask were transferred into a separatory funnel
7. extractionwhere the aqueous layer was extracted twice with EtOAc
8. washThe combined organics were washed with brine
9. dry with materialdried with magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. dissolutionThe crude material was dissolved in a small amount of ethanol
12. temperatureheated with a heat gun
13. temperatureafter 5 min cooled in an acetone dry ice bath
14. customThe solids were sonicated
15. filtrationcollected by filtration
16. concentrationThe mother liquor was concentrated