Synthesis
Under ice bath conditions, 5-carboxy-2-hydroxyindole (6.7 g) was slowly added to a stirred suspension of 30 mL of dichloroethane containing 23 g of aluminum chloride. Subsequently, chloroacetyl chloride (11.3 g) was added slowly and hydrogen chloride gas was released during the reaction. The reaction mixture was stirred for 10 minutes before being warmed to 40 to 50°C and maintained for 1.5 hours. The progress of the reaction was monitored by thin layer chromatography (Spreader: ethyl acetate, Stationary phase: silica gel) to confirm the complete consumption of the starting material. Upon completion of the reaction, the mixture was cooled to room temperature and carefully poured into ice water. The resulting precipitate was collected by vacuum filtration, washed well with water and dried under vacuum to give 10.3 g (98% yield) of the target product 5-chloroacetyl-2-hydroxyindole as an off-white solid.
References
[1] Journal of Medicinal Chemistry, 1991, vol. 34, # 6, p. 1860 - 1866
[2] Journal of Medicinal Chemistry, 1999, vol. 42, # 25, p. 5120 - 5130
[3] Patent: US6878733, 2005, B1. Location in patent: Page/Page column 172; 219
[4] Patent: US6350754, 2002, B2. Location in patent: Page column 23-24
[5] Journal of Heterocyclic Chemistry, 1991, vol. 28, # 6, p. 1525 - 1532
