Tert-butyl 3-bromo-6-chloropicolinate

Uses

1,1-Dimethylethyl Ester 3-Bromo-6-chloro-2-Pyridinecarboxylic Acid was used to study expeditious synthesis of isoquinolones and isocoumarins.

Synthesis

GENERAL STEPS: Toluenesulfonyl chloride (7.7 g, 40.4 mmol) was slowly added to a solution of tert-butanol (33 mL) containing 3-bromo-6-chloro-2-pyridinecarboxylic acid (4 g, 17 mmol) and pyridine (9.2 mL, 114 mmol) at 0 °C. The reaction mixture was then stirred continuously at room temperature for 12 hours. Upon completion of the reaction, saturated sodium bicarbonate solution was added and extracted with ethyl acetate (3 times). The organic phases were combined, washed with saturated brine and dried over anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure to afford the target product tert-butyl 3-bromo-6-chloropyridine-2-carboxylate (121A) in quantitative yield. The resulting product can be used in subsequent reactions without further purification. Product characterization data: 1H NMR (300 MHz, CDCl3) δ 7.85 (d, 1H), 7.26 (d, 1H), 1.63 (s, 9H).

References

[1] Patent: WO2010/80503, 2010, A1. Location in patent: Page/Page column 232-233
[2] Patent: WO2010/80503, 2010, A1. Location in patent: Page/Page column 199
[3] Patent: US2013/96120, 2013, A1. Location in patent: Paragraph 0878
[4] Patent: US2013/96121, 2013, A1. Location in patent: Paragraph 1224
[5] Patent: WO2014/28381, 2014, A1. Location in patent: Page/Page column 112