Synthesis
The general procedure for the synthesis of 6-bromochroman-2-one from hydrogenated cinnamic acid lactone is as follows: a solution of bromine (155 mL) in dichloromethane (500 mL) was slowly added dropwise to a solution of 3,4-dihydrocoumarin (450 g, 0.3 mol) in dichloromethane (2000 mL) over a period of 30 minutes. The reaction mixture was stirred overnight at 15 °C. After completion of the reaction, the reaction solution was diluted with dichloromethane (2000 mL) and washed sequentially with aqueous sodium bicarbonate (2 x 1000 mL) and water (1000 mL). The organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was washed with petroleum ether (2 x 500 mL), the filtrates were combined and concentrated. Finally, the target compound 6-bromochroman-2-one (BM1490) was obtained as white thick crystals (471 g, 74% yield) by recrystallization from a solvent mixture of dichloromethane/petroleum ether.
References
[1] Journal of Organometallic Chemistry, 1990, vol. 387, # 3, p. 381 - 390
[2] Patent: WO2017/49343, 2017, A1. Location in patent: Paragraph 0066
[3] Patent: EP3135667, 2017, A1. Location in patent: Paragraph 0425-0426
[4] Justus Liebigs Annalen der Chemie, 1884, vol. 226, p. 359
[5] Journal of Organic Chemistry, 1997, vol. 62, # 24, p. 8522 - 8528
