Diisopropylamine → HCID 19384700, compound

Participants

Reaction Steps

To a solution of LDA in THF (1 liter), which had been prepared from diisopropylamine (35 g) and a 1.6M solution of n-butyl lithium in hexane (216 ml), was added dropwise a solution of ethyl 2-(4-chlorophenyl)propionate (70 g) in THF (100 ml) which had been obtained in paragraph 1), at a temperature of -45° to -40° C. under an atmosphere of nitrogen gas. At the same temperature, the reaction mixture was stirred for 0.5 hours, and m-chlorobenzyl chloride (55.7 g) was added dropwise thereto. The mixture was subjected to the same post-treatment as described in paragraph 1), and the residue was dissolved in ethanol (700 ml). To this solution was added dropwise 40% aqueous sodium hydroxide (40 ml), followed by heating under reflux for 5 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting residue was added dropwise to 10% aqueous hydrochloric acid under ice-cooling, and extracted several times with dichloromethane. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting crystalline residue was washed with hexane to give 2 -(3-chlorobenzyl)-2-(4-chlorophenyl)propionic acid (yield, 93 g) as white crystals, m.p., 154.8° C.

Provenance & Evidence