Synthesis
To a solution of 5-chloro-1-indanone (500 g, 301.2 mmol) in tetrahydrofuran (THF, 500 mL), an aqueous solution (100 mL) of sodium borohydride (23.0 g, 602.4 mmol) was slowly added dropwise at a controlled temperature of between 0 °C and 100 °C for 1 hour. The reaction mixture was stirred at room temperature for 12 hours. After completion of the reaction, the reaction was quenched with water (500 mL) and extracted with ethyl acetate (3 x 1500 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford a racemic mixture of 5-chloro-2,3-dihydro-1H-inden-1-ol (48.0 g, 94.8% yield), which can be used directly in the next step of the reaction without further purification.
References
[1] Journal of the American Chemical Society, 2005, vol. 127, # 30, p. 10482 - 10483
[2] Patent: WO2017/147410, 2017, A1. Location in patent: Page/Page column 134; 135
[3] Bulletin de la Societe Chimique de France, 1973, p. 3096 - 3099
[4] Journal of Medicinal Chemistry, 2005, vol. 48, # 5, p. 1563 - 1575
[5] Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 1796 - 1805
