Synthesis
General procedure for the synthesis of (6-bromo-1H-indol-2-yl)methanol from 6-bromoindole-2-carboxylic acid: to a solution of 6-bromo-1H-indole-2-carboxylic acid (1.00 g, 4.20 mmol) in tetrahydrofuran (THF, 20.0 mL) was added slowly and dropwise at 0 °C lithium aluminium hydroxide (LiAlH4, 1.0 M solution in THF, 4.20 mL. 4.20 mmol). The reaction mixture was gradually warmed to room temperature with stirring for 4 hours. Upon completion of the reaction, the reaction was quenched by sequential addition of water and 15% aqueous sodium hydroxide (NaOH) solution at 0°C, at which time a precipitate was generated. The reaction mixture was filtered through a diatomaceous earth pad and the filtrate was extracted with ethyl acetate (EtOAc, 3 x 20 mL). The organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to afford the target product (6-bromo-1H-indol-2-yl)methanol (696 mg, 73% yield) as a yellow solid. The product was characterized by 1H NMR (500 MHz, CDCl3): δ 7.51 (s, 1H), 7.43 (d, J=8.0 Hz, 1H), 7.20 (dd, J=8.0,1.6 Hz, 1H), 6.38 (s, 1H), 4.83 (d, J=5.6 Hz, 2H).
References
[1] Liebigs Annalen der Chemie, 1986, # 3, p. 438 - 455
[2] Patent: US2012/157469, 2012, A1. Location in patent: Page/Page column 28-29
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 2, p. 364 - 377
