Chroman-8-carbaldehyde, 95%

Synthesis

68-12-2

206347-33-3

327183-32-4

Step B - Synthesis of compound 21C: n-Butyllithium (20 mL of 2.5 M toluene solution) was added dropwise to a mixed solution of anhydrous THF (240 mL) and hexane (40 mL) for compound 21B (10.9 g, 29.23 mmol) at -78 °C and anhydrous conditions. During the dropwise addition, it was ensured that the internal temperature of the reaction solution did not exceed 5°C. Subsequently, the reaction mixture was warmed to about 100 °C and stirred. n-Butyllithium (5.8 mL of 2.5 M toluene solution) diluted in 20 mL of hexane was slowly added at 5 °C and stirring was continued for 4 hours. After that, the mixture was stirred at 5 °C for 0.5 h. A solution of THF (10 mL) in dimethylformamide (3.38 mL, 43.84 mmol) was added. The reaction mixture was stirred at 5 °C for 10 min before warming up to room temperature and continued stirring for 0.5 h. The reaction was subsequently quenched with 1N HCl aqueous solution (100 mL). The organic and aqueous layers were separated and the aqueous layer was extracted with ether (3 x 200 mL). The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated in vacuum. The resulting residue was purified by Biotage 75-M silica gel column chromatography (elution gradient: 0 to 20% hexane solution of ethyl acetate) to afford compound 21C (4.20 g, 88% yield).1H NMR (400 MHz, CDCl3) δ: 10.41 (s, 1H), 7.64-7.63 (dd, J=1.5 Hz, 8.1 Hz. 1H), 7.25 (d, J=5.13Hz, 1H), 6.89 (t, J=7.3Hz, 1H), 4.30 (t, J=5.1Hz, 2H), 2.83 (t, J=6.2Hz, 2H), 2.09-2.03 (m, 2H).

References