Methanol → N-tert.-butyl-6-chloro-4-p-fluoro-phenyl-nicotinamide

Temperature

0 °C

14.1 ml (14.1 mMol) 4-Fluoro-phenylmagnesium chloride solution (IM in THF) were added over 10 minutes to a solution of 1.0 g (4.7 mMol) N-tert.-butyl-6-chloro-nicotinamide in 5.0 ml THF cooled to 0° C. and the reaction mixture was stirred 18 hours at 35° C. After cooling to 0° C., 1.14 ml (28.2 mMol) methanol were added over 20 minutes, followed, after 15 minutes, by 1.17 g (5.2 mMol) 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. After 30 minutes at room temperature, the brown solution was concentrated under reduced pressure to about 10 g, heated to 50° C. and 20 ml tert.-butyl-methylether were added. The resulting suspension was stirred 1 hour at 55° C., then 1 hour at room temperature and filtered. The filtrate was concentrated under reduced pressure and digested in 5 ml n-hexane/ethyl acetate 4:1 to yield 0.69 g (48%) N-tert.-butyl-6-chloro-4-p-fluoro-phenyl-nicotinamide as a light brown powder of m.p.=168-173° C.

1. temperatureAfter cooling to 0° C.
2. waitAfter 30 minutes at room temperature
3. concentrationthe brown solution was concentrated under reduced pressure to about 10 g
4. temperatureheated to 50° C.
5. addition20 ml tert.-butyl-methylether were added
6. stirringThe resulting suspension was stirred 1 hour at 55° C.
7. filtration1 hour at room temperature and filtered
8. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-4da20cb2522b46c9b3cb52d0667d03a0

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06297375B1