Synthesis
General procedure for the preparation of 2,3-dihydro-1H-indene-5-carboxaldehyde: Indane (15 g, 127 mmol) was dissolved in anhydrous dichloromethane (150 mL) under nitrogen protection and the solution was cooled to -30 °C. The solution was then purified by adding tin tetrachloride (50 g, 190 mmol, 1.5 equiv.). Subsequently, tin tetrachloride (50 g, 190 mmol, 1.5 eq.) was added all at once followed by a slow dropwise addition of 1,1-dichlorodimethyl ether (11.6 g, 127 mmol). After 20 minutes of reaction, the cooling bath was removed and the reaction mixture was gradually warmed up to room temperature. Afterwards, the reaction mixture was cooled again to 0 °C and the reaction was quenched by adding ice water (100 mL). The reaction mixture was extracted with ether (2 × 250 mL), and each extract was washed sequentially with water (2 × 100 mL), 5% aqueous HCl (50 mL) and saturated saline (2 × 100 mL). The organic phases were combined and dried with anhydrous sodium sulfate. The crude product was purified by silica gel column chromatography (eluent: heptane/ethyl acetate = 98:2) followed by ball-ball distillation (80 °C/0.005 mbar) to afford the target product 2,3-dihydro-1H-indene-5-carboxaldehyde as a colorless liquid (9.8 g, 51% yield, 97% purity). The structure of the product was confirmed by 13C-NMR and 1H-NMR: 13C-NMR (ppm): 192.22 (d), 152.01 (s), 145.26 (s), 135.29 (s), 128.86 (d), 125.15 (d), 124.79 (d), 33.17 (t), 32.37 (t), 25.34 (t ); 1H-NMR (ppm): 9.93 (s, 1H), 7.72 (s, 1H), 7.64 (m, 1H), 7.34 (m, 1H), 2.95 (t, J = 7 Hz, 4H), 2.12 (quintet, J = 7 Hz, 2H).
References
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 23, p. 3700 - 3706
[2] Patent: WO2015/821, 2015, A1. Location in patent: Page/Page column 8-9
[3] Journal of Organic Chemistry, 1974, vol. 39, # 19, p. 2852 - 2855
[4] Journal of Medicinal Chemistry, 1997, vol. 40, # 3, p. 322 - 330
