4-Methyl-4-pentenoic acid can be used as a pharmaceutical synthesis intermediate and an organic synthesis intermediate, mainly in laboratory research and development processes and chemical and pharmaceutical synthesis processes.
4-Methyl-4-pent-4-enoic acid was prepared as follows:
Step 1.Synthesis of ethyl 4-methyl-pent-4-enoate. To a room temperature solution of methyltriphenylphosphonium iodide (3.00 g, 7.38 mmol) in THF (25 mL) was added LiHMDS (1.0 M solution, 8.4 mL, 8.4 mmol). after 15 min the solution was cooled to -35 C and ethyl acetylpropionate (1.mL, 7.05 mmol) was added. The cooling bath was removed and the reaction was stirred for 40 min, then burst with water and extracted twice with EtOAc. The organic layers were combined, washed with water, brine, dried (Na2SO4), and concentrated in vacuum. The crude product was purified using rush chromatography on silica gel (3% EtOAc/hexane).
Step 2. Synthesis of 4-methyl-pent-4-enoic acid. To a solution of ethyl 4-methyl-pent-4-enoate (530 mg, 3.73 mmol) in EtOH (5 mL) was added 1NaOH (10 mL). The mixture was stirred for 3 days, concentrated in vacuum to remove ethanol and diluted with H2O and Et2O. The layers were separated and the organic layer was washed once with water. The aqueous layers were combined, acidified to pH 1 with 1NHCl and extracted twice with Et2O. The organic layers were combined, washed with brine, dried (Na2SO4) and concentrated in vacuum to give 4-methyl-4-pentenoic acid.
