Formaldehyde → 1-(3-Fluoro-benzyl)-4-(1-methyl-piperidin-4-yl)-1H-indole-2-carboxylic acid amide

Participants

Reaction Steps

To a solution of 1-(3-Fluoro-benzyl)-4-piperidin-4-yl-1H-indole-2-carboxylic acid amide (50 mg, 0.14 mmol) in CH2Cl2 (5 ml) were added formaldehyde (20 μl, 0.24 mmol, 37% in H2O solution) and NaBH(OAc)3 (74 mg, 0.35 mmol). After stirring at room temperature for 4 hours, the reaction mixture was added to a saturated solution of sodium bicarbonate, followed by a mixture of CH2Cl2/H2O. The organic fraction was separated, washed with water and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo to give 1-(3-Fluoro-benzyl)-4-(1-methyl-piperidin-4-yl)-1H-indole-2-carboxylic acid amide as a brown oil. This oil was dissolved in 4 ml ethanol, and 2 M ethanolic hydrochloric acid solution (1 ml) was added. The reaction mixture is heated at 100° C. for 20 minutes, then cooled to room temperature, and 14 mg of 1-(3-Fluoro-benzyl)-4-(1-methyl-piperidin-4-yl)-1H-indole-2-carboxylic acid amide hydrochloride salt was collected. MS: 366 (M+H)+.

Provenance & Evidence