2-(4-chlorophenyl)-2-methylpropanenitrile

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

Procedure: Diisobutylaluminum hydride (0.236 mol, 236 mL of a 1M solution in hexane) is added over 90 minutes to a solution of p-chloro-α-methylhydratroponitrile (32.6 g, 0.181 mol) in diethyl ether under nitrogen at 0° C. After the addition is complete, water and 6N hydrochloric acid are added to the reaction mixture while maintaining the temperature below 30° C. The resultant aqueous solution is stirred overnight at room temperature and extracted with diethyl ether The organic extracts are combined, washed sequentially with 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give the title product as an oil (31.1 g, 94% yield). After the addition while maintaining the temperature below 30° C extracted with diethyl ether The organic extracts washed sequentially with 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (p-chlorophenyl)acetonitrile (30.32 g, 0.20 mol) in tetrahydrofuran is treated dropwise with lithium diisopropylamide (0.44 mol, 220 mL of a 2M solution in heptane/tetrahydrofuran/benzene) at -25° C. to -30° C., over 60 minutes under nitrogen, stirred at -15° C. for one hour, treated dropwise with a solution of iodomethane (62.45 g, 0.44 mol) in tetrahydrofuran at -15° C., stirred at -15° C. for one hour, and diluted with water. The aqueous solution is extracted with ether. The organic extract is washed sequentially with water, 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oily residue. The residue is distilled to give the title product as a colorless oil (32.6 g, bp 89-91° C./1 mm Hg, 90.7% yield). stirred at -15° C. for one hour The aqueous solution is extracted with ether The organic extract is washed sequentially with water, 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo to obtain an oily residue The residue is distilled

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (p-chlorophenyl)acetonitrile (30.32 g, 0.20 mol) in tetrahydrofuran is treated dropwise with lithium diisopropylamide (0.44 mol, 220 mL of a 2M solution in heptane/tetrahydrofuran/benzene) at -25° C. to -30° C., over 60 minutes under nitrogen, stirred at -15° C. for one hour, treated dropwise with a solution of iodomethane (62.45 g, 0.44 mol) in tetrahydrofuran at -15° C., stirred at -15° C. for one hour, and diluted with water. The aqueous solution is extracted with ether. The organic extract is washed sequentially with water, 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oily residue. The residue is distilled to give the title product as a colorless oil (32.6 g, bp 89-91° C./1 mm Hg, 90.7% yield). stirred at -15° C. for one hour The aqueous solution is extracted with ether The organic extract is washed sequentially with water, 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo to obtain an oily residue The residue is distilled

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

Procedure: Diisobutylaluminum hydride (0.236 mol, 236 mL of a 1 M solution in hexane) is added over 90 minutes to a solution of p-chloro-α-methylhydratroponitrile (32.6 g, 0.181 mol) in diethyl ether under nitrogen at 0° C. After the addition is complete, water and 6 N hydrochloric acid are added to the reaction mixture while maintaining the temperature below 30° C. The resultant aqueous solution is stirred overnight at room temperature and extracted with diethyl ether. The organic extracts are combined, washed sequentially with 2 N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give the title product as an oil (31.1 g, 94% yield). After the addition while maintaining the temperature below 30° C extracted with diethyl ether washed sequentially with 2 N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (p-chlorophenyl)acetonitrile (30.32 g, 0.20 mol) in tetrahydrofuran is treated dropwise with lithium diisopropylamide (0.44 mol, 220 mL of a 2 M solution in heptane/tetrahydrofuran/benzene) at −25° C. to −30° C. over 60 minutes under nitrogen, stirred at −15° C. for one hour, treated dropwise with a solution of iodomethane (62.45 g, 0.44 mol) in tetrahydrofuran at −15° C., stirred at −15° C. for one hour, and diluted with water. The aqueous solution is extracted with ether. The organic extract is washed sequentially with water, 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oily residue. The residue is distilled to give the title product as a colorless oil (32.6 g, bp 89-91° C./1 mm Hg, 90.7% yield) stirred at −15° C. for one hour The aqueous solution is extracted with ether The organic extract is washed sequentially with water, 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo to obtain an oily residue The residue is distilled

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

Procedure: To a solution of 2-(4-chlorophenyl)-2-methylpropionitrile (243 mg, 1.4 mmol) in benzene (1.4 mL) was added slowly at 50° C. under an atmosphere of nitrogen and with stirring to a 2.8 M solution of ethylmagnesium chloride in tetrahydrofuran (1.45 ml, 4.1 mmol). The reaction mixture was heated to reflux for 2 h, and thereafter, cooled and poured onto 10% aqueous ammonium chloride solution (4 mL). The organic layer was separated and treated with 2 N aqueous hydrochloric acid solution (1 mL). The reaction was heated to reflux for 1 h. After cooling the reaction mixture was diluted with water and extracted twice with benzene. The organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using heptane/ethyl acetate (9:1 v/v) as eluent to give the title compound (64 mg, 20%) as a pale-yellow oil. The reaction mixture was heated to reflux for 2 h cooled The organic layer was separated treated with 2 N aqueous hydrochloric acid solution (1 mL) The reaction was heated to reflux for 1 h After cooling the reaction mixture was diluted with water extracted twice with benzene The organic layer was washed with brine dried over sodium sulfate evaporated under reduced pressure The residue was purified by column chromatography on silica gel

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

Procedure: Diisobutylaluminum hydride (0.236 mol, 236 mL of a 1M solution in hexane) is added over 90 minutes to a solution of p-chloro-α-methylhydratroponitrile (32.6 g, 0.181 mol) in diethyl ether under nitrogen at 0° C. After the addition is complete, water and 6N hydrochloric acid are added to the reaction mixture while maintaining the temperature below 30° C. The resultant aqueous solution is stirred overnight at room temperature and extracted with diethyl ether. The organic extracts are combined, washed sequentially with 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give the title product as an oil (31.1 g, 94% yield). After the addition while maintaining the temperature below 30° C extracted with diethyl ether washed sequentially with 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (p-chlorophenyl)acetonitrile (30.32 g, 0.20 mol) in tetrahydrofuran is treated dropwise with lithium diisopropylamide (0.44 mol, 220 mL of a 2M solution in heptane/tetrahydrofuran/benzene) at -25° C. to -30° C. over 60 minutes under nitrogen, stirred at -15° C. for one hour, treated dropwise with a solution of iodomethane (62.45 g, 0.44 mol) in tetrahydrofuran at -15° C., stirred at -15° C. for one hour, and diluted with water. The aqueous solution is extracted with ether The organic extract is washed sequentially with water, 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oily residue. The residue is distilled to give the title product as a colorless oil (32.6 g, bp 89°-91° C./1 mm Hg, 90.7% yield). stirred at -15° C. for one hour The aqueous solution is extracted with ether The organic extract is washed sequentially with water, 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo to obtain an oily residue The residue is distilled

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

Procedure: Diisobutylaluminum hydride (0.236 mol, 236 mL of a 1M solution in hexane) is added over 90 minutes to a solution of p-chloro-α-methylhydratroponitrile (32.6 g, 0.181 mol) in diethyl ether under nitrogen at 0° C. After the addition is complete, water and 6N hydrochloric acid are added to the reaction mixture while maintaining the temperature below 30° C. The resultant aqueous solution is stirred overnight at room temperature and extracted with diethyl ether The organic extracts are combined, washed sequentially with 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give the title product as an oil (31.1 g, 94% yield). After the addition while maintaining the temperature below 30° C extracted with diethyl ether The organic extracts washed sequentially with 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (p-chlorophenyl)acetonitrile (30.32 g, 0.20 mol) in tetrahydrofuran is treated dropwise with lithium diisopropylamide (0.44 mol, 220 mL of a 2M solution in heptane/tetrahydrofuran/benzene) at -25° C. to -30° C., over 60 minutes under nitrogen, stirred at -15° C. for one hour, treated dropwise with a solution of iodomethane (62.45 g, 0.44 mol) in tetrahydrofuran at -15° C., stirred at -15° C. for one hour, and diluted with water. The aqueous solution is extracted with ether. The organic extract is washed sequentially with water, 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oily residue. The residue is distilled to give the title product as a colorless oil (32.6 g, bp 89-91° C./1 mm Hg, 90.7% yield). stirred at -15° C. for one hour The aqueous solution is extracted with ether The organic extract is washed sequentially with water, 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo to obtain an oily residue The residue is distilled