1,3-dihydro-4-methyl-2H-imidazol-2-one → Ethyl 2,3-dihydro-5-methyl-epsilon-2-dioxo-1H-imidazole-4-hexanoate

Participants

Reaction Conditions

Reaction Steps

A slurry of this crude intermediate [containing 10.6 g (0.108 mol) of 4-methyl-4-imidazolin-2-one by assay] in 51.8 g of sulfolane and 100 ml of chloroform was cooled to ice bath temperature in a 3-necked round bottom flask equipped with reflux condenser, nitrogen inlet, nitrogen outlet, mechanical stirrer and addition funnel and 71.8 g (0.540 mol) of AlCl3 added portionwise. After the addition was complete, the temperature of the bath was raised to 75° C. and 29.0 g (0.151 mol) of ethyl 5-ethoxycarbonylpentanoyl chloride added dropwise over a 60 minute period. On heating an additional 1.5 hours, tlc (silica gel, methanol/ethyl acetate 1:4, UV followed by phosphomolybdic acid visualization) suggested the complete consumption of starting material and the formation of the desired ketoester. The reaction mixture was then poured onto 500 ml of ice containing 16 g of sodium carbonate dissolved in 50 ml of water. The aqueous hydrolysis mixture was stirred rapidly while 400 ml of ethyl ether was added. After 15 minutes the precipitated solid was removed by filtration, washed with ether and dried overnight under vacuum to afford 30.0 g of tan solid shown to be 76% pure by hplc analysis (83% yield corrected for purity). The solid was recrystallized from 1:1 ethanol:water to yield 16.7 g of purified title product, homogeneous by hplc and tlc, m.p. 170°-172° C., identical in physical properties to the product of the preceding Example.

Provenance & Evidence