Synthesis
General procedure for the synthesis of isoquinoline-3-carbaldehyde from methyl isoquinoline-3-carboxylate: methyl isoquinoline-3-carboxylate (2.0 g, 10.7 mmol) was dissolved in toluene and the solution was cooled to -78 °C. Diisobutylaluminum hydride (1 M solution in toluene, 21.4 mL, 21.4 mmol) was slowly added to this solution using a syringe over a period of 15 minutes. Keeping the reaction mixture at -78 °C, the reaction was quenched with a mixture of ether (80 mL), acetic acid (20 mL) and water (8 mL). The mixture was then slowly warmed to room temperature and stirred overnight. The organic layer was separated and the solvent was evaporated. Purification by fast column chromatography (eluent gradient: 1:4 ethyl acetate/hexane to 1:3 ethyl acetate/hexane) afforded 1.1 g of the title compound isoquinoline-3-carbaldehyde in 65% yield.1H-NMR (CDCl3, 300 MHz) δ 10.24 (s, 1H), 9.35 (s, 1H), 8.36 (s, 1H), 8.07- 7.98 (m, 2H), 7.82-7.32 (m, 2H). MS: m/z 158 ([MH]+).
References
[1] Patent: WO2005/56550, 2005, A2. Location in patent: Page/Page column 75-76
[2] Patent: WO2005/92885, 2005, A1. Location in patent: Page/Page column 73
[3] Patent: WO2005/56562, 2005, A1. Location in patent: Page/Page column 71-72
[4] Tetrahedron Letters, 1999, vol. 40, # 6, p. 1211 - 1214
[5] Patent: US5554620, 1996, A
