Formaldehyde → 4-Methyl-2-methylene valeric acid

Participants

Reaction Steps

To neat ethyl isobutylmalonate (25 g, 0.13 mol) at 0 C. was slowly added ice cold diethylamine (15.1 mL, 0.15 mol). After stirring for 15 minutes, formalin (11.1 mL of 37% aqueous formaldehyde) was added dropwise and the mixture was allowed to stir at 25° C. for 3 days. The reaction was treated with a solution of 20 g of K2CO3 in 40 mL of H2O and extracted with ether (2×100 mL). The combined ether layers were washed with brine, dried over MgSO4, and evaporated at 20° C. on a rotary evaporator. The crude product ethyl 4-methyl-2-methylenepentanoate (containing some ether) was dissolved in 250 mL of absolute ethanol and treated with acetonitrile (250 mL), 1M LiOH (9.7 g in 250 mL of H2O, 0.23 mol). After stirring overnight, the organic solvents were evaporated and the aqueous residue was extracted with ethyl acetate (2×150 mL). The combined extracts were washed with brine, dried (MgSO4), and evaporated to afford 10.5 g of 4-methyl-2-methylenepentanoic acid as a colorless oil.

Provenance & Evidence