5-methyl-1H-Indole-2-methanol synthesis

Yield:55795-87-4 98%

Reaction Conditions:

with lithium aluminium tetrahydride in tetrahydrofuran at 0 - 20;Inert atmosphere;

Steps:

2.1. Typical procedure for the preparation of (1H-indol-2-yl)methanols: synthesis of the (1H-indol-2-yl)methanol

General procedure: A flame dried three-necked round bottom flask, equipped with a magnetic stirring bar, was charged with ethyl 1H-indole-2-carboxylate (1.5 g, 7.93 mmol, 1.0 equiv.) dissolved in anhydrous THF (20 mL) under argon. Then, a solution of LiAlH₄ in THF (2 M, 4.4 mL, 8.72 mmol, 1.1 equiv.) was added dropwise at 0°C and the mixture was stirred for 1 hour. After this time, the mixture was allowed to warm to room temperature and stirred until the disappearance of the starting material, monitoring by TLC (mobile phase for TLC: n-hexane-EtOAc, 80:20). The reaction was cooled down to 0°C and quenched with an 80 percent aqueous MeOH solution. The mixture was extracted with CH₂Cl₂, washed with a solution of KHSO₄ (10% w/w) and with brine. The organic layer was dried over MgSO₄, filtered, and concentrated under reduced pressure. The resulting crude product was used in the next step without further purification (1.108 g, 95% yield).

References:

Arcadi, Antonio;Calcaterra, Andrea;Chiarini, Marco;Fabrizi, Giancarlo;Fochetti, Andrea;Goggiamani, Antonella;Iazzetti, Antonia;Marrone, Federico;Marsicano, Vincenzo;Serraiocco, Andrea [Synthesis,2021,vol. 54,# 3,p. 741 - 753] Location in patent:supporting information