2-(2-fluorophenyl)-2-methylpropanenitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 2-(2-Fluorophenyl)-2-methylpropionitrile (0.211 g) was magnetically stirred with aqueous solutions of 5N sodium hydroxide (2 mL), 55% tetrabutylammonium hydrogensulfate (0.1 mL) and 30% hydrogen peroxide (3 mL) for 22 hours. The reaction mixture was diluted with toluene and extracted. The aqueous phase was neutralized with 5% hydrochloric acid and extracted twice with ethyl acetate. The combined organic extracts were washed with water, then brine, and dried over anhydrous magnesium sulfate. Filtration and evaporation gave 2-(2-fluorophenyl)isobutyramide as a pale-green oil that solidified on standing (0.173 g). GC/MS: m/z 181 (RT 9.80 min.). 1H-NMR (DMSO-d6): 7.39-7.27 (m, 2H), 7.19-7.07 (m, 2H), 6.83 and 6.78 (2 s, CONH2), 1.43 (s, 6H) extracted extracted twice with ethyl acetate The combined organic extracts were washed with water brine, and dried over anhydrous magnesium sulfate Filtration and evaporation

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

Procedure: 2-(2-Fluorophenyl)-2-methylpropionitrile (0.211 g) was magnetically stirred with aqueous solutions of 5N sodium hydroxide (2 mL), 55% tetrabutylammonium hydrogensulfate (0.1 mL) and 30% hydrogen peroxide (3 mL) for 22 hours. The reaction mixture was diluted with toluene and extracted. The aqueous phase was neutralized with 5% hydrochloric acid and extracted twice with ethyl acetate. The combined organic extracts were washed with water, then brine, and dried over anhydrous magnesium sulfate. Filtration and evaporation gave 2-(2-fluorophenyl)isobutyramide as a pale-green oil that solidified on standing (0.173 g). GC/MS: m/z 181 (RT 9.80 min.). 1H-NMR (DMSO-d6): 7.39-7.27 (m, 2H), 7.19-7.07 (m, 2H), 6.83 and 6.78 (2 s, CONH2), 1.43 (s, 6H) extracted extracted twice with ethyl acetate The combined organic extracts were washed with water brine, and dried over anhydrous magnesium sulfate Filtration and evaporation

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To an oven dried, N2 purged 250 mL round bottom flask attached with addition funnel was added 4-bromoaniline (7.31 g, 42.5 mmol) and anhydrous toluene (40 mL). To the reaction solution at 0° C. was added a 2.0 M Me3Al (32 mL, 1.5 molar equiv) solution. The reaction solution was stirred at 0° C. for 30 min, then a solution of 2-(2-fluorophenyl)-2-methylpropanenitrile (7.62 g, 46.7 mmol) in toluene (25 mL) was added to the reaction flask. The reaction solution was allowed to stir at 90° C. for 5 hr. The cooled reaction solution was quenched with an aq sodium potassium tartrate solution. After standing 20 min, the organic phase was partitioned and washed with sodium potassium tartrate solution. The organic solution was extracted with 1N aq HCl (100 mL×3). The combined aq HCl solution was neutralized by addition of 1N aq NaOH and extracted with dichloromethane (200 mL×2). The dichloromethane product solution was dried over Na2SO4, filtered, and concentrated in vacuo to afford the title compound (5.5 g, 39% yield). GCMS m/z=334, 336 [M]+. To an oven dried N2 purged 250 mL round bottom flask attached with addition funnel to stir at 90° C. for 5 hr The cooled reaction solution was quenched with an aq sodium potassium tartrate solution After standing 20 min the organic phase was partitioned washed with sodium potassium tartrate solution The organic solution was extracted with 1N aq HCl (100 mL×3) The combined aq HCl solution was neutralized by addition of 1N aq NaOH extracted with dichloromethane (200 mL×2) The dichloromethane product solution was dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: 2-(2-Fluorophenyl)-2-methylpropionitrile (0.211 g) was magnetically stirred with aqueous solutions of 5N sodium hydroxide (2 mL), 55% tetrabutylammonium hydrogensulfate (0.1 mL) and 30% hydrogen peroxide (3 mL) for 22 hours. The reaction mixture was diluted with toluene and extracted. The aqueous phase was neutralized with 5% hydrochloric acid and extracted twice with ethyl acetate. The combined organic extracts were washed with water, then brine, and dried over anhydrous magnesium sulfate. Filtration and evaporation gave 2-(2-fluorophenyl)isobutyramide as a pale-green oil that solidified on standing (0.173 g). GC/MS: m/z 181 (RT 9.80 min.). 1H-NMR (DMSO-d6): 7.39-7.27 (m, 2H), 7.19-7.07 (m, 2H), 6.83 and 6.78 (2 s, CONH2), 1.43 (s, 6H) extracted extracted twice with ethyl acetate The combined organic extracts were washed with water brine, and dried over anhydrous magnesium sulfate Filtration and evaporation