Chemical Properties
Methyl 6-bromo-1H-indazole-3-carboxylate is an ester compound with a molecular weight of 255.07, a density of 1.709±0.06 g/cm
3 and a boiling point of 399.7 °C (760 mm Hg), which is an irritant to the skin and eyes, and is also acutely toxic.
Uses
Methyl 6-bromo-1H-indazole-3-carboxylate is an organic intermediate compound used in chemical and laboratory research, as an organic synthetic material or reaction reagent.It can be used to synthesize its downstream products (Methyl 6-bromo-1-methyl-1H-indazole 3-carboxylate) and other ester compounds.
Synthesis
Concentrated sulfuric acid (1.50 mL, 28 mmol) was slowly added to a methanolic (50 mL, 1 mol) suspension of 6-bromo-1H-indazole-3-carboxylic acid (3.00 g, 12 mmol), and the reaction mixture was heated to 90°C and held for 4 hours. After completion of the reaction, it was cooled to room temperature and the mixture was diluted with 200 mL of ethyl acetate and washed sequentially with 150 mL of saturated aqueous sodium bicarbonate and 150 mL of brine. The organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 2.42 g (76% yield) of methyl 6-bromo-1H-indazole-3-carboxylate as a yellow solid. The product was dissolved in tetrahydrofuran (50 mL), cooled to 0 °C and sodium hydride (0.417 g, 10.4 mmol) was added in batches. After stirring at 0 °C for 30 min, [β-(trimethylmethylsilyl)ethoxy]methyl chloride (1.85 mL, 10.4 mmol) was added slowly and dropwise. The reaction mixture was slowly warmed to room temperature over 90 min, excess sodium hydride was quenched by the addition of methanol and concentrated under reduced pressure. The residue was diluted with 200 mL of ethyl acetate and washed with 200 mL of brine. The aqueous phase was back-extracted with 50 mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Purification by CombiFlash Fast Chromatography System (40g silica gel column; dissolved in dichloromethane; elution gradient: 100:0 to 50:50 heptane:ethyl acetate, 30 min) gave 3.22 g (88% yield) of the target compound as a yellow oil.
References
[1] Patent: WO2013/24011, 2013, A1. Location in patent: Page/Page column 51
[2] Patent: WO2011/50245, 2011, A1. Location in patent: Page/Page column 134-135
[3] Patent: WO2011/20615, 2011, A1. Location in patent: Page/Page column 85; 86
