N-bromobutanimide → 2-Amino-5-bromo-3-fluoropyridine

To a solution of 2-amino-3-fluoro-pyridine (9.4 g, 83.1 mmol, 1 eq.) in MeCN (470 mL) under argon at 0° C. was added NBS (7.4 g, 41.5 mmol, 0.5 eq.). The reaction mixture was stirred at r.t. for 1 h then cooled to 0° C. before introducing additional NBS (7.39 g, 41.5 mmol, 0.5 eq.). The reaction mixture was stirred at r.t. for 1 h then diluted in EtOAc. The organic layer was washed with a saturated NaHCO3 solution, dried over Na2SO4, filtered and concentrated in vacuo. The residue was diluted in DCM, washed with a 1 N NaOH solution. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo to afford Intermediate Gen-1-a (2-amino-5-bromo-3-fluoropyridine).

1. temperaturethen cooled to 0° C.
2. stirringThe reaction mixture was stirred at r.t. for 1 h
3. washThe organic layer was washed with a saturated NaHCO3 solution
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. additionThe residue was diluted in DCM
8. washwashed with a 1 N NaOH solution
9. dry with materialThe organic phase was dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-7179f0dbda3b48288998cb91d7f09781

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249141B2