4-ISOPROPYLPHENYLACETONITRILE

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

Procedure: In a 250 ml flask, 4-isopropylphenylacetonitrile 8.00 g (50.2 mmol) was dissolved in tetrahydrofuran (150 ml) under a nitrogen atmosphere. The solution was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 52.8 ml (52.8 mmol) added. The resulting mixture was stirred at −78° C. for 1 hour. To this reaction mixture was added iodomethane 3.29 ml (52.8 mmol). The resulting mixture was slowly allowed to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid and extracted twice with diethyl ether. The organic fractions were combined, dried (MgSO4) and concentrated under vacuo. Chromatography (SiO2, 20% ethyl acetate/hexanes) gave 6.32 g (73%) of the title compound. to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid extracted twice with diethyl ether dried (MgSO4) concentrated under vacuo

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

Procedure: In a 250 ml flask, 4-isopropylphenylacetonitrile 8.00 g (50.2 mmol) was dissolved in tetrahydrofuran (150 ml) under a nitrogen atmosphere. The solution was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 52.8 ml (52.8 mmol) added. The resulting mixture was stirred at −78° C. for 1 hour. To this reaction mixture was added iodomethane 3.29 ml (52.8 mmol). The resulting mixture was slowly allowed to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid and extracted twice with diethyl ether. The organic fractions were combined, dried (MgSO4) and concentrated under vacuo. Chromatography (SiO2, 20% ethyl acetate/hexanes) gave 6.32 g (73%) of the title compound. to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid extracted twice with diethyl ether dried (MgSO4) concentrated under vacuo

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

Procedure: In a 250 ml flask, 4-isopropylphenylacetonitrile 8.00 g (50.2 mmol) was dissolved in tetrahydrofuran (150 ml) under a nitrogen atmosphere. The solution was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 52.8 ml (52.8 mmol) added. The resulting mixture was stirred at −78° C. for 1 hour. To this reaction mixture was added iodomethane 3.29 ml (52.8 mmol). The resulting mixture was slowly allowed to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid and extracted twice with diethyl ether. The organic fractions were combined, dried (MgSO4) and concentrated under vacuo. Chromatography (SiO2, 20% ethyl acetate/hexanes) gave 6.32 g (73%) of the title compound. to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid extracted twice with diethyl ether dried (MgSO4) concentrated under vacuo

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

Procedure: In a 250 ml flask, 4-isopropylphenylacetonitrile 8.00 g (50.2 mmol) was dissolved in tetrahydrofuran (150 ml) under a nitrogen atmosphere. The solution was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 52.8 ml (52.8 mmol) added. The resulting mixture was stirred at −78° C. for 1 hour. To this reaction mixture was added iodomethane 3.29 ml (52.8 mmol). The resulting mixture was slowly allowed to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid and extracted twice with diethyl ether. The organic fractions were combined, dried (MgSO4) and concentrated under vacuo. Chromatography (SiO2, 20% ethyl acetate/hexanes) gave 6.32 g (73%) of the title compound. to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid extracted twice with diethyl ether dried (MgSO4) concentrated under vacuo

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

Procedure: To a solution of 4-isopropylphenylacetonitrile (2 g, 12.5 mmol) in anhydrous ether (50 mL) was added absolute ethanol (0.5 g, 12.5 mmol) and an excess of HCl gas was passed into the solution with cooling in an ice bath. The resulting solution was allowed to stir at 0° C. for 1.5 hours and at room temperature overnight. The white solid was collected by filtration, washed with ether (2×20 mL) and dried to give 2.52 g (84%) of 4-isopropylphenylacetimidate hydrochloride as white crystals, mp 118-120° C. A solution of ethylenediamine (1.25 g, 20 mmol) in absolute ethanol (5 mL) was added to a solution of the imidate hydrochloride (2.5 g, 10 mmol) in absolute ethanol (15 mL) cooled at ice-bath temperature. After stirring at 0° C. for 1 hour, the solution was heated at reflux for 20 minutes. The solvent was evaporated and the oily residue was washed with water (2×3 mL) and extracted with methylene chloride (3×15 mL). The solution was dried (MgSO4), filtered and evaporated under reduced pressure to afford 2 g of the free base of the title compound. A solution of the free base in anhydrous ether was treated with dry HCl gas. The crude salt was collected and recrystallized from ethanol/ether to give 1.95 g (79%) of the title compound as a white solid. mp 176-178° C.; Anal. C13H18N2.HCl: C, H, N. with cooling in an ice bath The white solid was collected by filtration washed with ether (2×20 mL) dried

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

Procedure: To a solution of 4-isopropylphenylacetonitrile (2 g, 12.5 mmol) in anhydrous ether (50 mL) was added absolute ethanol (0.5 g, 12.5 mmol) and an excess of HCl gas was passed into the solution with cooling in an ice bath. The resulting solution was allowed to stir at 0° C. for 1.5 hours and at room temperature overnight. The white solid was collected by filtration, washed with ether (2×20 mL) and dried to give 2.52 g (84%) of 4-isopropylphenylacetimidate hydrochloride as white crystals, mp 118-120° C. A solution of ethylenediamine (1.25 g, 20 mmol) in absolute ethanol (5 mL) was added to a solution of the imidate hydrochloride (2.5 g, 10 mmol) in absolute ethanol (15 mL) cooled at ice-bath temperature. After stirring at 0° C. for 1 hour, the solution was heated at reflux for 20 minutes. The solvent was evaporated and the oily residue was washed with water (2×3 mL) and extracted with methylene chloride (3×15 mL). The solution was dried (MgSO4), filtered and evaporated under reduced pressure to afford 2 g of the free base of the title compound. A solution of the free base in anhydrous ether was treated with dry HCl gas. The crude salt was collected and recrystallized from ethanol/ether to give 1.95 g (79%) of the title compound as a white solid. mp 176-178° C.; Anal. C13H18N2.HCl: C, H, N. with cooling in an ice bath The white solid was collected by filtration washed with ether (2×20 mL) dried

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 100 g of 4-isopropylbenzyl chloride in 1500 mL of N,N-dimethylformamide was added 32.0 g of sodium cyanide under ice-cooling. The mixture was stirred at 70° C. for 4 hours, and water was added to the reaction mixture. The mixture was extracted with ethyl acetate, and the organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 96.5 g of (4-isopropylphenyl)acetonitrile. cooling The mixture was extracted with ethyl acetate the organic layer was washed with water and brine dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure

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

Procedure: In a 250 ml flask, 4-isopropylphenylacetonitrile 8.00 g (50.2 mmol) was dissolved in tetrahydrofuran (150 ml) under a nitrogen atmosphere. The solution was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 52.8 ml (52.8 mmol) added. The resulting mixture was stirred at −78° C. for 1 hour. To this reaction mixture was added iodomethane 3.29 ml (52.8 mmol). The resulting mixture was slowly allowed to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid and extracted twice with diethyl ether. The organic fractions were combined, dried (MgSO4) and concentrated under vacuo. Chromatography (SiO2, 20% ethyl acetate/hexanes) gave 6.32 g (73%) of the title compound. to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid extracted twice with diethyl ether dried (MgSO4) concentrated under vacuo

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

Procedure: In a 250 ml flask, 4-isopropylphenylacetonitrile 8.00 g (50.2 mmol) was dissolved in tetrahydrofuran (150 ml) under a nitrogen atmosphere. The solution was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 52.8 ml (52.8 mmol) added. The resulting mixture was stirred at −78° C. for 1 hour. To this reaction mixture was added iodomethane 3.29 ml (52.8 mmol). The resulting mixture was slowly allowed to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid and extracted twice with diethyl ether. The organic fractions were combined, dried (MgSO4) and concentrated under vacuo. Chromatography (SiO2, 20% ethyl acetate/hexanes) gave 6.32 g (73%) of the title compound. to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid extracted twice with diethyl ether dried (MgSO4) concentrated under vacuo

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

Procedure: In a 250 ml flask, 4-isopropylphenylacetonitrile 8.00 g (50.2 mmol) was dissolved in tetrahydrofuran (150 ml) under a nitrogen atmosphere. The solution was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 52.8 ml (52.8 mmol) added. The resulting mixture was stirred at −78° C. for 1 hour. To this reaction mixture was added iodomethane 3.29 ml (52.8 mmol). The resulting mixture was slowly allowed to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid and extracted twice with diethyl ether. The organic fractions were combined, dried (MgSO4) and concentrated under vacuo. Chromatography (SiO2, 20% ethyl acetate/hexanes) gave 6.32 g (73%) of the title compound. to warm to ambient temperature over 16 hours then quenched with 0.2M hydrochloric acid extracted twice with diethyl ether dried (MgSO4) concentrated under vacuo

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 100 g of 4-isopropylbenzyl chloride in 1500 mL of N,N-dimethylformamide was added 32.0 g of sodium cyanide under ice-cooling. The mixture was stirred at 70° C. for 4 hours, and water was added to the reaction mixture. The mixture was extracted with ethyl acetate, and the organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 96.5 g of (4-isopropylphenyl)acetonitrile. cooling The mixture was extracted with ethyl acetate the organic layer was washed with water and brine dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 100 g of 4-isopropylbenzyl chloride in 1500 mL of N,N-dimethylformamide was added 32.0 g of sodium cyanide under ice-cooling. The mixture was stirred at 70° C. for 4 hours, and water was added to the reaction mixture. The mixture was extracted with ethyl acetate, and the organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 96.5 g of (4-isopropylphenyl)acetonitrile. cooling The mixture was extracted with ethyl acetate the organic layer was washed with water and brine dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure