[Synthesis]
Under nitrogen protection, 4-bromoisoquinoline (2.0 g, 9.6 mmol) was dissolved in 30 mL of redistilled tetrahydrofuran (THF) and cooled to -65°C. n-Butyllithium (4.0 mL, 10 mmol, 2.5 M solution in THF) was added slowly and dropwise. Maintaining this temperature, the reaction mixture was stirred for 30 min. Subsequently, N,N-dimethylformamide (730 mg, 10 mmol) was added dropwise and stirring was continued for 1 h at the same temperature. After completion of the reaction, 100 mL of saturated aqueous ammonium chloride solution was added to the mixture. The reaction mixture was extracted with ethyl acetate (50 mL × 3). The organic layers were combined, washed with 100 mL of brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (elution gradient: 0-100% ethyl acetate/petroleum ether) to give isoquinoline-4-carboxaldehyde (550 mg, yellow solid, yield: 36%).1H NMR (400 MHz, CDCl3): δ 10.41 (s, 1H), 9.45 (s, 1H), 9.22 (d, J = 8.4 Hz, 1H) 8.96 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.96-7.92 (m, 1H), 7.76 (t, J = 8.4 Hz, 1H). |
[References]
[1] Tetrahedron, 1998, vol. 54, # 35, p. 10317 - 10328
[2] European Journal of Organic Chemistry, 2009, # 26, p. 4458 - 4467
[3] Patent: US2017/37050, 2017, A1. Location in patent: Paragraph 0346-0349 |