Synthesis
General procedure for the synthesis of 2-hydroxymethyl-6-chloroindole from ethyl 6-chloroindole-2-carboxylate: 2.00 g (8.94 mmol) of ethyl 6-chloroindole-2-carboxylate was dissolved in 50 ml of ethyl ether at 0°C, and 0.475 g (12.5 mmol) of lithium aluminum hydride was added slowly. The reaction mixture was heated to 45°C to reflux the reaction. Upon completion of the reaction, 10 ml of water, 10 ml of 2M aqueous sodium hydroxide solution and 10 ml of water were added sequentially at 0°C to quench the reaction. The aqueous layer was separated and extracted with tert-butyl methyl ether (3 x 100 ml). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product 2-hydroxymethyl-6-chloroindole (1.64 g; 100% yield) as a white solid. MS data: MS m/e (relative abundance): 180 ([M-H]+, 100).
References
[1] Patent: US2007/27173, 2007, A1. Location in patent: Page/Page column 112
[2] Patent: US2008/161315, 2008, A1. Location in patent: Page/Page column 15
[3] Patent: US2007/27163, 2007, A1. Location in patent: Page/Page column 22
[4] Journal of Medicinal Chemistry, 2007, vol. 50, # 6, p. 1380 - 1400
[5] Patent: US2003/144282, 2003, A1
