N-bromobutanimide → 2-Bromo-5-bromomethylpyridine

To a slurry of 2-bromo-5-methylpyridine (10.29 g) and N-bromosuccinimide (5.32 g) in carbon tetrachloride (150 mL) was added AIBN (200 mg) and the reaction vessel was purged with nitrogen. The reaction mixture was heated, under reflux, for 1.5 h then allowed to cool to room temperature. The reaction mixture was filtered and the filtrate was concentrated in vacuo to give 2-bromo-5-(bromomethyl)pyridine (4 g). This, together with tert-butyl 2-(diphenylmethyleneamino)acetate (4.71 g) and (2S,4S,5R)-2-((R)-allyloxy(quinolin-4-yl)methyl)-1-(anthracen-9-ylmethyl)-5-vinyl-1-azoniabicyclo[2.2.2]octane bromide (1.073 g) was dissolved in DCM (100 mL) and the solution was cooled to −78° C. under nitrogen. 2-tert-Butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine (5 mL) was added dropwise over 5 min and the mixture was stirred at −78° C. for 7 h then allowed to reach RT overnight. The reaction mixture was concentrated in vacuo and partitioned between ethyl acetate and water. The ethyl acetate was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The material obtained, (S)-tert-butyl 3-(6-bromopyridin-3-yl)-2-(diphenylmethyleneamino)propanoate (6 g), was dissolved in THF (75 mL) and to the solution was added citric acid (22 g) in water (75 mL). The mixture was stirred vigorously for 6 h then concentrated in vacuo and loaded onto an SCX cartridge. The cartridge was washed with water then methanol. The product was eluted with 10% ammonia in methanol. The solvent was removed in vacuo to give the sub-title compound (4.0 g).

1. customthe reaction vessel was purged with nitrogen
2. temperatureThe reaction mixture was heated
3. temperatureunder reflux, for 1.5 h
4. filtrationThe reaction mixture was filtered
5. concentrationthe filtrate was concentrated in vacuo

ORD record

ord-d66ebd18d8df4a0b9f60d9b4dbb03184

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902181B2