Acetaldehyde → Gramine

Participants

Reaction Conditions

Reaction Steps

To a solution of indole (46.8 g, 0.40 mmol) in glacial AcOH (200 mL) at 0° C. under a nitrogen blanket was added isopropylamine (37.6 mL, 0.44 mol) over a period of 10 minutes. To a cold solution was added a solution of acetaldehyde (22.4 mL, 0.44 mL) in benzene (60 mL) over 30 minutes. The resulting brown solution was stirred at 0° C. for 24 hours, after which the reaction mixture was poured into 400 mL of ice water. The mixture was extracted with Et2O (3×200 mL). The combined ether extracts were extracted with 0.5 N HCl (3×150 mL) and the combined aqueous extracts were washed with Et2O (2×200 mL). The combined aqueous extracts were cooled to 0° C., then made basic with 50% aqueous NaOH to pH 12. The precipitate was extracted with CH2Cl2 (3×300 mL) and the combined extracts were washed with brine (200 mL), dried over Na2SO4, filtered, and the solvent was removed under reduced pressure to afford Intermediate 15 as a yellow semisolid (30 g, 37%): TLC Rf (1:1 CH2Cl2/EtOAc)=0.11.

Provenance & Evidence