Methyl iodide → N-methyl-L-tryptophan

Participants

Reaction Steps

The protected tryptophan derivative from above (0.573 g, 1.00 mmol) was dissolved in DMF (3 mL) and the solution cooled in ice. Sodium hydride (60% oil dispersion, 0.048 g, 1.2 mmol) was added and the mixture stirred for 30 min. Iodomethane (0.093 mL, 1.5 mmol) was added and stirring continued for an additional hour. The reaction was then quenched with 10% citric acid (2 mL) and water (25 mL), and extracted with Et2O (100 mL). The extract was dried (MgSO4) and concentrated, and the residue purified by flash chromatography (20-30% EtOAc/hexane as eluent) to give the desired N-methyltryptophan derivative (0.284 g). The N-methyltryptophan derivative from above (0.711 g, 1.21 mmol) was dissolved in MeOH (10 mL) and thionyl chloride (0.6 mL) was added dropwise. The mixture was heated to 60° C. for 3 h. Volatiles were removed under reduced pressure and the residue triturated with TBME (25 mL). The precipitated white solid was collected, washed with TBME and dried to give N-methyl-5-hydroxytryptophan methyl ester hydrochloride (0.339 g). MS (ES+) m/z 249 (MH+). The methyl ester hydrochloride from above (0.170 g, 0.6 mmol) was suspended in concentrated aqueous ammonia (15 mL) and the mixture was stirred overnight at room temperature. Volatiles were then removed under vacuum and the residue triturated with MeOH (34 mL) and Et2O (15 mL). The amide derivative was obtained as a brown solid (0.136 g).

Provenance & Evidence