Methyl phenylacetate → Methyl 3-cyano-2-phenylpropanoate

Participants

Reaction Steps

A solution of methyl phenylacetate (200 g, 1.33 mol) in THF (300 mL) is added, dropwise, to a -78° C. solution of lithium diethylamide (LDA, 1.4 mol) in THF (2500 mL). After addition is complete, a precipitate forms, and additional THF (200 mL) is added. The resulting mixture is vigorously stirred while a solution of bromoacetonitrile (168 g, 1.4 mol) in THF (400 mL) is slowly added. After 20 minutes the cooling bath is removed and the reaction mixture is quenched with saturated NH4Cl solution (500 mL). After allowing the mixture to slowly warm to ambient temperature any solid material is removed by filtration and the solvent is removed in vacuo. The residue is dissolved in ET2O (1000 mL) and diluted with H2O (1000 mL). The organic phase is then washed with 0.5N HCl (1×1000 mL), saturated NaCl solution (2×1000 mL) and concentrated in vacuo. The residue is then vacuum distilled (~1 mm Hg) and the fraction boiling between 125° C. and 145° C. is collected to give β-(carbomethoxy)-β-phenylpropionitrile which solidifies upon standing.

Provenance & Evidence