Iodine → N-(5-Fluoro-4-iodo-pyridin-3-yl)-2,2-dimethyl-propionamide

Temperature

-78 °C

A 2.5M solution of nBuLi (30.6 mL, 76 mmol) in hexanes was added drop-wise to a solution of N-(5-fluoropyridin-3-yl)-2,2-dimethylpropanamide 5.0 g, 25.5 mmol) and TMEDA (11.54 mL, 76 mmol) in THF (127 mL) at −78° C. over 1 hour, while ensuring the internal temperature did not go above −70° C. The resulting solution was stirred at −78° C. for 1 hour. Iodine (19.40 g, 76 mmol) in THF (20 mL) was added drop-wise over 30 min ensuring the internal temperature remained below −70° C. The resulting reaction was stirred for 1 hour at −78° C. The reaction was quenched at −78° C. with water and then warmed to ambient temperature. 10% Aqueous sodium thiosulfate was added until the iodine color dissipated and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure to afford the title compound (8.21 g, 25.5 mmol, 100% yield), MS (ESI): m/z=323.26 (MH+), 100% pure by LCMS.

1. customdid not go above −70° C
2. customremained below −70° C
3. customThe resulting reaction
4. stirringwas stirred for 1 hour at −78° C
5. customThe reaction was quenched at −78° C. with water
6. temperaturewarmed to ambient temperature
7. addition10% Aqueous sodium thiosulfate was added until the iodine color
8. extractionthe mixture was extracted with ethyl acetate (×3)
9. dry with materialThe combined organic fractions were dried (MgSO4)
10. filtrationfiltered
11. customthe solvent was evaporated under reduced pressure

ORD record

ord-9d365d3c13e747609c5791cfa9f0ca6c

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315475B2