Phenylacetic Acid → HCID 19969608, compound

Participants

Reaction Steps

A 2.5M hexane solution of butyl lithium (440 ml) was added over 1 hour to an ice-cooled solution of phenylacetic acid (70 g, 0.51 mol), hexamethyl-phosphoramide (91 ml) and THF (tetrahydrofuran, 0.81). The reaction mixture was allowed to warm to room temperature over 1.5 hours, then cooled back to 0° C. A solution of methyl iodide (33 ml, 0.52 mol) in THF (100 ml) was added to the stirred reaction and after 15 minutes at 0° C., then 1.5 hours at room temperature the reaction was cooled back to 0° C. and butyl lithium (220 ml of a 2.5M hexane solution) was added dropwise. The reaction was stirred at 0° C. for 10 minutes and room temperature for 0.5 hour. After cooling to 0° C., a solution of picolyl chloride (0.61 mol) in THF (100 ml) was added over 0.5 hour. The ice bath was removed and the reaction was stirred overnight at room temperature. The reaction mixture was partitioned between water and ethyl acetate. The basic aqueous layer was neutralized at 0° C. with 3N HCl and the precipitated solids were filtered, washed with ether and dried to give the subtitle acid (52 g). Extraction of the aqueous filtrate with ethyl acetate and concentration of the ethyl acetate layer afforded a crude residue. The residue was triturated with ether to give an additional 25 g of product.

Provenance & Evidence