Diisopropylamine → 3-Ethoxy-4-ethoxycarbonylphenylacetic acid

Participants

Reaction Conditions

Reaction Steps

Under an atmosphere of nitrogen, n-butyllithium (25 ml, 15% w/w solution in hexane) was added to a solution of diisopropylamine (3.6 g) in tetrahydrofuran (30 ml) at −30° C. The mixture was stirred at −30° C. for 30 minutes, cooled to −75° C., and hexamethylphosphoramide (HMPA, 10 g) was added slowly. A solution of ethyl 2-ethoxy-4-methylbenzoate (5 g) in tetrahydrofuran (10 ml) was then added at −75° C. and the mixture was stirred for two hours. Carbon dioxide gas was then purged into the reaction mixture at −75° C. till complete decolorization. The reaction mixture was then stirred at −75 to −70° C. for 30 minutes and then brought to 10° C., diluted with water (50 ml), and extracted with ether. The aqueous layer was acidified with 10% aqueous sulphuric acid to pH ˜2 and extracted with dichloromethane. The combined dichloromethane layer was washed with water and concentrated in vacuo. The oily product so obtained was re-dissolved in ether (50 ml) and washed with water. The ethereal layer was then concentrated in vacuo to afford a thick oil which solidified on keeping at room temperature to afford 3-ethoxy-4-(ethoxycarbonyl)phenyl acetic acid 4.4 g (72.7%).

Provenance & Evidence