ethyl 3-cyano-2-phenylpropanoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In this example 42 g of 3-trifluoromethylbenylacetic acid in 100 ml of tetrahydrofuran was added to a cooled slurry containing 9.65 g of sodium hydride in 50 ml of tetrahydrofuran. The resulting mixture was allowed to stand for about 15-18 hours at room temperature, under a nitrogen atmosphere. The mixture was cooled to 0° C. and then 201 ml of a 1 molar solution of lithium bis[trimethylsilyl]amide in tetrahydrofuran was added. This mixture was stirred for 20 minutes at 0° C. and then 20.4 g of (α-ethoxycarbonylbenzyl)acetonitrile in 50 ml of tetrahydrofuran was added. The mixture was stirred and allowed to warm toward room temperature for 11/2 hours, and then added to 1,200 ml of water at room temperature. The aqueous mixture was extracted twice with petroleum ether. The extracts were combined and concentrated under vacuum, to a white paste. The solids were collected by suction filtration and dissolved in methylene chloride. The solution was washed once with aqueous 10% hydrochloric acid; twice with saturated aqueous sodium bicarbonate, dried over magnesium sulfate and evaporated yielding 17.2 g of the title compound as a white solid. 2.2 g of this solid was further purified by recrystallization from methanol, MP 111° to 112° C. The mixture was stirred to warm toward room temperature for 11/2 hours The aqueous mixture was extracted twice with petroleum ether concentrated under vacuum, to a white paste The solids were collected by suction filtration dissolved in methylene chloride The solution was washed once with aqueous 10% hydrochloric acid twice with saturated aqueous sodium bicarbonate, dried over magnesium sulfate evaporated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In this example 10 g of ethyl phenylacetate in 10 ml of THF was added dropwise to 61 ml of a 1 molar solution lithium bis[trimethylsilvllamide in tetrahydrofuran, under nitrogen, at -78° C. The mixture was stirred for one hour at -78° C. A solution containing 10.2 g of iodoacetonitrile in 10 ml of tetrahydrofuran was added dropwise. The reaction mixture was stirred at -78° C. for about one-half hour and then stirred for two hours and allowed to warm toward room temperature during this period. The reaction mixture was then added to water and the pH adjusted to pH 1 by the addition of aqueous 10% hydrochloric acid. The mixture was washed with saturated aqueous sodium chloride solution and extracted three times with ethyl ether. The extracts were combined, washed twice with aqueous saturated sodium bicarbonate, dried over magnesium sulfate and evaporated affording 10.7 g of the title compound is an oil. The oil was further purified by chromatography over silica gel eluting with 20% vol. ethyl acetate petroleum ether. was added dropwise The reaction mixture was stirred at -78° C. for about one-half hour stirred for two hours to warm toward room temperature during this period The mixture was washed with saturated aqueous sodium chloride solution extracted three times with ethyl ether washed twice with aqueous saturated sodium bicarbonate dried over magnesium sulfate evaporated