Methanol → 3-Bromo-N-phenyl-4-pyridinecarboxamide

Temperature

-69 °C

As described in Synthetic Communications 1997, 27, 1075-1086, a 4-necked RBF equipped with an overhead stirrer and a J-Kem internal temperature probe was placed N-phenylisonicotinamide (35.7 g, 0.18 mol) and anhydrous THF (700 ml). All material appeared to go into solution. This mixture was cooled to −69° C. in a dry ice/IPA bath. To this was slowly added nBuLi (158 ml of a 2.5 M solution in Hexanes) in three portions. While adding the first equivalent of nBuLi, an exotherm was observed raising the temperature to ca. −41° C. The orange reaction mixture was slightly heterogeneous. This was allowed to slowly warm to −5 to 0° C. over 1.5 hrs in a ice/brine bath. The reaction mixture was recooled to −72° C. and 1,2-dibromoethane (36 g, 0.189 mol) in 15 ml of THF was added. A slight exotherm was observed rising to −62° C. The reaction mixture was allowed to stir overnight. The reaction mixture was poured into a flask containing 10 vol. SiO2. Methanol (100 ml) was added and the mixture was concentrated under reduced pressure. The dried silica gel was then placed on top of a bed of silica gel. The plug of silica gel was washed with 40% ethyl acetate/Hexane as eluent. Concentration of 10 liters of solvent afforded an off-white solid. The material was placed in vacuum drying at 60° C. overnight to provide 34 g (68% th) of an off-white solid.

1. customa 4-necked RBF equipped with an overhead stirrer
2. temperaturean exotherm was observed raising the temperature to ca. −41° C
3. temperatureto slowly warm to −5 to 0° C. over 1.5 hrs in a ice/brine bath
4. customwas recooled to −72° C.
5. customwas observed rising to −62° C
6. additionThe reaction mixture was poured into a flask
7. additioncontaining 10 vol. SiO2
8. concentrationthe mixture was concentrated under reduced pressure
9. washThe plug of silica gel was washed with 40% ethyl acetate/Hexane as eluent
10. customConcentration of 10 liters of solvent afforded an off-white solid
11. customdrying at 60° C. overnight
12. customto provide 34 g (68% th) of an off-white solid

ORD record

ord-36bb7f6eea9a4a94866108a992b73fc2

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07709677B2