Iodine → N-(5-Fluoro-3-iodopyridin-2-yl)-2,2-dimethylpropanamide

Temperature

-78 °C

To a solution of 33 g of freshly distilled N-(5-fluoro-pyridin-2-yl)-2,2-dimethyl-propionamide (0.168 mol) in 500 mL tert-butylmethylether at −78° C. was added dropwise 323 mL of a ca. 1.3 M solution of sec BuLi (0.42 mol) in cyclohexane at a rate that the temperature did not exceed −60° C. (liquid nitrogen cooling; ca 5 min). The mixture was stirred at −78° C. for 30 min. To the resulting light yellow suspension was added dropwise a solution of 107 g iodine (0.420 mol) in 150 mL tetrahydrofuran at a rate that the temperature did not exceed −65° C. (liquid nitrogen cooling; ca 5 min). The mixture was then stirred at −78° C. for 2 h. To the resulting suspension was added a 10% sodium thiosulfate solution in water (800 mL) and the phases were separated. The organic phase was washed with a 10% solution of sodium thiosulfate in water, 10% citric acid solution in water, 10% sodium bicarbonate solution in water and brine, dried over magnesium sulfate and concentrated under aspirator vacuum whereby crystallisation occurred. The solid was collect by filtration and washed with cyclohexane and air-dried to constant weight.

1. customdid not exceed −60° C.
2. custom(liquid nitrogen cooling; ca 5 min)
3. customdid not exceed −65° C.
4. custom(liquid nitrogen cooling; ca 5 min)
5. stirringThe mixture was then stirred at −78° C. for 2 h
6. customthe phases were separated
7. washThe organic phase was washed with a 10% solution of sodium thiosulfate in water, 10% citric acid solution in water
8. dry with material10% sodium bicarbonate solution in water and brine, dried over magnesium sulfate
9. concentrationconcentrated under aspirator vacuum whereby crystallisation
10. filtrationThe solid was collect by filtration
11. washwashed with cyclohexane
12. customair-dried to constant weight

ORD record

ord-2a872886f1984fcbab6da62f15435d12

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07208494B2