31241-19-7

2,3,3-Trimethyl-5-methoxy-3H-indole is used as a key intermediate in the synthesis of the spirane copper ion sensor SP1 [1].

2,3,3-Trimethyl-5-methoxy-3H-indole was prepared by refluxing 4-methoxyphenylhydrazine hydrochloride with 3-methylbutan-2-one in a solution of glacial acetic acid for 5.5 hours. The specific reaction steps are as follows: 4-methoxyphenylhydrazine hydrochloride (4.815 g, 27.57 mmol) was added to a solution containing 3-methylbutan-2-one (5.90 mL, 55.2 mmol) in glacial acetic acid (88 mL). The solution was stirred at reflux for 5.5 h. The solution was allowed to cool to room temperature and neutralized with KOH pellets. The crude material was extracted with Et2O (3 × 100 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (70:30, hexanes/ EtOAc) to afford 2,3,3-trimethyl-5-methoxy-3H-indole as a red amorphous solid (5.149 g, 99%) [1].

[1] Trevino, K. M., Tautges, B. K., Kapre, R. (2021). Highly Sensitive and Selective Spiropyran-Based Sensor for Copper(II) Quantification. ACS Omega, 6 16, 10776–10789. https://doi.org/10.1021/acsomega.1c00392