Synthesis
General procedure for the synthesis of 3-amino-6-methoxy-2-bromopyridine from 5-amino-2-methoxypyridine:
1. 1.83 g (14.7 mmol) of 5-amino-2-methoxypyridine, 1.21 g (14.7 mmol) of sodium acetate, and 12 mL of acetic acid were sequentially added to a reaction flask and stirred well.
2. 0.75 mL (14.7 mmol) of bromine was slowly added dropwise at room temperature, keeping the reaction at room temperature. 3.
3. After the dropwise addition, continue to stir the reaction mixture at room temperature for 30 minutes. 4.
4. Upon completion of the reaction, 200 mL of saturated sodium thiosulfate solution was added to the reaction mixture to quench the reaction.
5. The reaction mixture was transferred to a partition funnel and the aqueous phase was extracted twice with ethyl acetate.
6. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 3 g of the purple solid product 3-amino-6-methoxy-2-bromopyridine (quantitative yield).
Product characterization data: 1H NMR (250 MHz, DMSO-d6) δ: 7.18 (d, 1H), 6.64 (d, 1H), 4.91 (s, 2H), 3.71 (s, 3H).
References
[1] Patent: US2008/200495, 2008, A1. Location in patent: Page/Page column 9
[2] Tetrahedron Letters, 2011, vol. 52, # 41, p. 5292 - 5296
[3] Journal of Medicinal Chemistry, 1995, vol. 38, # 24, p. 4830 - 4838
[4] Patent: WO2005/30213, 2005, A1. Location in patent: Page/Page column 170-171
[5] Patent: US5366972, 1994, A
