Synthesis
General procedure for the synthesis of 6-(benzyloxy)nicotinaldehyde from 2-benzyloxy-5-bromopyridine and N,N-dimethylformamide: n-butyllithium (2.5 M hexane solution, 2.61 mL, 1.05 eq.) was slowly added to a tetrahydrofuran solution (25 mL, -78 °C) of 2-benzyloxy-5-bromopyridine (1.64 g, 6.2 mmol). After 1 hour of reaction at -78 °C, N,N-dimethylformamide (0.97 mL, 2 eq.) was added and stirring was continued at -78 °C for 30 minutes. The reaction mixture was rapidly poured into a stirring 5% aqueous sodium bicarbonate solution (50 mL) and extracted with ether (3 x 50 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated to give a crude product of 1.16 g (quantitative yield), which could be used in the next reaction without further purification. Mass spectrometry analysis showed a molecular ion peak of 186.34 ([MH]+) for the target compound.
References
[1] Patent: WO2003/104236, 2003, A1. Location in patent: Page 169
[2] Polyhedron, 2013, vol. 52, p. 755 - 760
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2536 - 2548
[4] Patent: WO2004/92145, 2004, A1. Location in patent: Page 149
[5] Patent: US2009/82403, 2009, A1. Location in patent: Page/Page column 66
