Methyl phenylacetate → Methyl 3-cyano-2-phenylpropanoate

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.

1. customto a -78° C.
2. additionAfter addition
3. additionis slowly added
4. customAfter 20 minutes the cooling bath is removed
5. customthe reaction mixture is quenched with saturated NH4Cl solution (500 mL)
6. customis removed by filtration
7. customthe solvent is removed in vacuo
8. dissolutionThe residue is dissolved in ET2O (1000 mL)
9. additiondiluted with H2O (1000 mL)
10. washThe organic phase is then washed with 0.5N HCl (1×1000 mL), saturated NaCl solution (2×1000 mL)
11. concentrationconcentrated in vacuo
12. distillationvacuum distilled (~1 mm Hg)
13. customboiling between 125° C. and 145° C.
14. customis collected

ORD record

ord-57d648a061e246a7a4f3fbb82ade528a

Source dataset

uspto-grants-2000_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06043365