Formaldehyde → 2-methyl-6-nitro-2,3,4,9-tetrahydro-1H-beta-carboline

Participants

Reaction Steps

Under N2, formaldehyde (0.56 ml of a 36.5% aqueous solution, 7.3 mmol) was added to a solution of 5-nitro-3-(2-methylaminoethyl)-1H-indole (1.6 g, 7.3 mmol) in glacial acetic acid (10 mL). After 20 h of stirring at room temperature, the mixture was refluxed for 2 h and taken to dryness in vacuo. The residue was treated with H2O (150 mL) and EtOAc (150 mL) and then basified by the addition of 2M NaOH. The organic phase was separated and the aqueous layer was reextracted with three portions of EtOAc. The combined organic solution was extracted with 10% aqueous H2SO4 (3×160 mL). The acidic aqueous phase was cooled in an ice bath, basified with concentrated aqueous NaOH and extracted with tert-butyl methyl ether (4×175 mL). The dried (Na2SO4) extract was evaporated to dryness to afford 1.40 g of 2-methyl-6-nitro-2,3,4,9-tetrahydro-1H-β-carboline that were used directly in the next step.

Provenance & Evidence