Synthesis
General procedure for the synthesis of 2-bromothiazole-5-methanol from 2-bromo-5-formylthiazole: 2-bromothiazole-5-formaldehyde (3.00 g, 15.62 mmol) was mixed with methanol (50 mL). The mixture was cooled to 0 °C under nitrogen protection and sodium borohydride (0.591 g, 15.62 mmol) was added in batches. The reaction was stirred at this temperature for 2 hours. Subsequently, the reaction system was slowly warmed to room temperature and stirring was continued for 2 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure. To the residue, saturated aqueous ammonium chloride solution was added, and the pH was adjusted to about 6 with 1 M aqueous hydrochloric acid, and then adjusted to about 10 with 1 M aqueous sodium hydroxide. the mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with saturated brine, dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography eluting with a gradient of ethyl acetate/hexane (10% to 25%) to give 2-bromothiazole-5-methanol as a light yellow oil. Mass spectrum (DCI+) m/z 194,196 (M+H)+.
References
[1] Patent: WO2012/87833, 2012, A1. Location in patent: Page/Page column 125-126
[2] Journal of Medicinal Chemistry, 2007, vol. 50, # 25, p. 6303 - 6306
[3] Patent: WO2004/37818, 2004, A1. Location in patent: Page 69 - 70
[4] Patent: WO2007/75749, 2007, A2. Location in patent: Page/Page column 25; 37-39
[5] Patent: WO2009/77990, 2009, A1. Location in patent: Page/Page column 92
