METHYL (2-CYANOPHENYL)ACETATE

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

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

Procedure: 1.5 g of tetra-n-butylammonium bromide, 6.5 g of 1,2-dibromoethane and 20 mL of aqueous 50% sodium hydroxide solution were added to a toluene (40 mL) solution of 4.0 g of methyl 2-cyanophenylacetate, and stirred at room temperature for 1 hour. Water was added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The crude product was purified through silica gel column chromatography (hexane/ethyl acetate) to obtain 3.0 g of the entitled compound as a colorless compound. 1H-NMR (400 MHz, CDCl3) δ: 7.66 (1H, dd, J=7.6, 1.2 Hz), 7.55 (1H, td, J=7.6, 1.2 Hz), 7.43-7.36 (2H, m), 3.66 (3H, s), 1.82 (2H, q, J=3.7 Hz), 1.30 (2H, q, J=3.7 Hz) ESI-MS Found: m/z [M+H] 202. extracted with ethyl acetate The organic layer was washed with saturated saline water dried with anhydrous magnesium sulfate the solvent was evaporated away under reduced pressure The crude product was purified through silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: 1.5 g of tetra-n-butylammonium bromide, 6.5 g of 1,2-dibromoethane and 20 mL of aqueous 50% sodium hydroxide solution were added to a toluene (40 mL) solution of 4.0 g of methyl 2-cyanophenylacetate, and stirred at room temperature for 1 hour. Water was added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The crude product was purified through silica gel column chromatography (hexane/ethyl acetate) to obtain 3.0 g of the entitled compound as a colorless compound. 1H-NMR (400 MHz, CDCl3) δ: 7.66 (1H, dd, J=7.6, 1.2 Hz), 7.55 (1H, td, J=7.6, 1.2 Hz), 7.43-7.36 (2H, m), 3.66 (3H, s), 1.82 (2H, q, J=3.7 Hz), 1.30 (2H, q, J=3.7 Hz) ESI-MS Found: m/z [M+H] 202. extracted with ethyl acetate The organic layer was washed with saturated saline water dried with anhydrous magnesium sulfate the solvent was evaporated away under reduced pressure The crude product was purified through silica gel column chromatography (hexane/ethyl acetate)

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

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

Procedure: A diethyl ether solution (38 mL) of 2 M ethylmagnesium bromide was dropwise added at room temperature to a diethyl ether (200 mL) solution of methyl 2-cyanophenylacetate (10 g) and titanium tetraisopropoxide (17.9 g), and stirred for 1 hour. Aqueous 1 N hydrochloric acid solution was added to the reaction liquid, and the organic layer was separated. The aqueous layer was extracted with chloroform, the organic layer was washed with saturated saline water, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure. The crude product was purified through basic silica gel column chromatography (hexane/ethyl acetate) to give the entitled compound as a colorless solid (1.8 g). the organic layer was separated The aqueous layer was extracted with chloroform the organic layer was washed with saturated saline water dried with anhydrous magnesium sulfate The solvent was evaporated away under reduced pressure The crude product was purified through basic silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: Tetra-n-butylammonium bromide (1.5 g), 1,2-dibromoethane (6.5 g) and aqueous 50% sodium hydroxide solution (20 mL) were added to a toluene (40 mL) solution of methyl 2-cyanophenylacetate (4.0 g), and stirred at room temperature for 1 hour. Water was added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, then dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The crude product was purified through silica gel column chromatography (hexane/ethyl acetate) to give the entitled compound as a colorless solid (3.0 g). extracted with ethyl acetate The organic layer was washed with saturated saline water dried with anhydrous magnesium sulfate the solvent was evaporated away under reduced pressure The crude product was purified through silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: 1.5 g of tetra-n-butylammonium bromide, 6.5 g of 1,2-dibromoethane and 20 mL of aqueous 50% sodium hydroxide solution were added to a toluene (40 mL) solution of 4.0 g of methyl 2-cyanophenylacetate, and stirred at room temperature for 1 hour. Water was added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The crude product was purified through silica gel column chromatography (hexane/ethyl acetate) to obtain 3.0 g of the entitled compound as a colorless compound. extracted with ethyl acetate The organic layer was washed with saturated saline water dried with anhydrous magnesium sulfate the solvent was evaporated away under reduced pressure The crude product was purified through silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: 1.5 g of tetra-n-butylammonium bromide, 6.5 g of 1,2-dibromoethane and 20 mL of aqueous 50% sodium hydroxide solution were added to a toluene (40 mL) solution of 4.0 g of methyl 2-cyanophenylacetate, and stirred at room temperature for 1 hour. Water was added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The crude product was purified through silica gel column chromatography (hexane/ethyl acetate) to obtain 3.0 g of the entitled compound as a colorless compound. extracted with ethyl acetate The organic layer was washed with saturated saline water dried with anhydrous magnesium sulfate the solvent was evaporated away under reduced pressure The crude product was purified through silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: To a solution of 3a in methanol (0.2 M) was added palladium, 10 weight % (dry basis) on activated carbon, wet, (0.1 eq) and concentrated hydrochloric acid (3.5 eq). The reaction mixture was shaken overnight on a Parr reactor, with hydrogen pressure equal to 70 psi. The reaction mixture was filtered through celite, concentrated in vacuo then triturated with ether. The product was obtained as a white solid. (85%) 1H NMR (300 MHz, DMSO-d6) δ 8.66 (br s, 2H), 7.55 (m, 1H), 7.32 (m, 3H), 4.01 (m, 2H), 3.89 (s, 2H), 3.61 (s, 3H). palladium, 10 weight % (dry basis) on activated carbon The reaction mixture was filtered through celite concentrated in vacuo then triturated with ether The product was obtained as a white solid

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

Procedure: To a stirring solution of copper (I) cyanide (1.2 eq) in dimethylformamide (2.1 M) at room temperature was added slowly a solution of 2a in dimethylformamide (8.7 M). The reaction was heated to reflux overnight then cooled to room temperature. A solution of iron (III) chloride (1.2 eq) in H2O (0.3 M) was added slowly to the vigorously stirred solution. The resulting solution was extracted with ethyl acetate (3×). The organic phases were combined then washed with brine (1×), dried over sodium sulfate, filtered, concentrated in vacuo and purified by flash chromatography (15% ethyl acetate/hexanes) to afford the product as a clear oil. (70%) 1H NMR (300 MHz, CDCl3) δ 6.09 (m, 1H), 5.98 (m, 1H), 5.79 (m, 2H), 2.29 (s, 2H), 2.11 (s, 3H). The reaction was heated to reflux overnight The resulting solution was extracted with ethyl acetate (3×) The organic phases were combined then washed with brine (1×) dried over sodium sulfate filtered concentrated in vacuo purified by flash chromatography (15% ethyl acetate/hexanes)

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

Procedure: 1.5 g of tetra-n-butylammonium bromide, 6.5 g of 1,2-dibromoethane and 20 mL of aqueous 50% sodium hydroxide solution were added to a toluene (40 mL) solution of 4.0 g of methyl 2-cyanophenylacetate, and stirred at room temperature for 1 hour. Water was added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The crude product was purified through silica gel column chromatography (hexane/ethyl acetate) to obtain 3.0 g of the entitled compound as a colorless compound. 1H-NMR (400 MHz, CDCl3) δ: 7.66 (1H, dd, J=7.6, 1.2 Hz), 7.55 (1H, td, J=7.6, 1.2 Hz), 7.43-7.36 (2H, m), 3.66 (3H, s), 1.82 (2H, q, J=3.7 Hz), 1.30 (2H, q, J=3.7 Hz) ESI-MS Found: m/z [M+H] 202. extracted with ethyl acetate The organic layer was washed with saturated saline water dried with anhydrous magnesium sulfate the solvent was evaporated away under reduced pressure The crude product was purified through silica gel column chromatography (hexane/ethyl acetate)