Synthesis
Step 1: Synthesis of ethyl 6-bromoquinoline-3-carboxylate
To a solution of 5-bromo-2-nitrobenzaldehyde (2 g, 9 mmol) in ethanol (46 mL) was sequentially added tin(II) chloride dihydrate (7.95 g, 35.2 mmol) and ethyl 3,3-diethoxypropionate (4.2 mL, 22 mmol). The reaction mixture was heated to 90 °C and maintained for 16 hours. Upon completion of the reaction, it was cooled to room temperature and stirring was continued overnight. Subsequently, the reaction mixture was concentrated and the residue was dissolved in ethyl acetate. The solution was poured into a saturated aqueous sodium bicarbonate solution to form an emulsion. The emulsion was filtered through diatomaceous earth and the diatomaceous earth was rinsed with ethyl acetate. The organic and aqueous layers were separated and the aqueous phase was further extracted with ethyl acetate. All organic phases were combined, washed with brine, dried over magnesium sulfate, filtered and concentrated. Finally, purification by fast column chromatography (eluent: 0-50% ethyl acetate/heptane gradient) gave ethyl 6-bromoquinoline-3-carboxylate (1.41 g, 60% yield) as a solid.
References
[1] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3488 - 3491
[2] Patent: US2012/270893, 2012, A1. Location in patent: Page/Page column 32
