Diethyl (ethoxymethylene)malonate → Ethyl 2-((Acetyloxy)methyl)-8-iodo-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]-quinoline-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of diethyl ethoxymethylenemalonate (2.73 mL) and (5-iodo-2,3-dihydro-1H-indol-2-yl)methyl acetate (Preparation 8, 3.90 g) is heated to 120° C. under a stream of nitrogen. After starting material is consumed, the mixture is cooled and diluted with EtOAc. The crude product is chromatographed eluting with 20, 40, and 60% EtOAc in heptane (500 mL each) to give 5.28 g (88%) of the corresponding enamine as a brown oil. A portion of this material (4.61 g) is dissolved in Eaton's Reagent (10 mL) and heated to 80° C. for 1 h. Upon cooling, the crude mixture is poured into a cold beaker and a 50% NaOH solution is slowly added until pH=7. The cloudy solution is then poured into CH2Cl2. The organic layer is separated and washed with brine, dried (Na2SO4), filtered, and concentrated to give a brown solid. The crude product is chromatographed eluting with 0-4% methanol in CH2Cl2 to give 880 mg (21%) of the title compound as a brown solid. Physical characteristics: MS (ESI+) m/z 442 (M+H)+, 464 (M+Na)+.

Provenance & Evidence