3-(2,4-dichlorophenyl)-3-oxopropanenitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 43.8 g of ethyl 2,4-dichloro-benzoate and 8.2 g of anhydrous acetonitrile is added dropwise to a suspension of 6.1 g of 80% strength sodium hydride in 100 ml of anhydrous tetrahydrofuran in the course of about 1 hour under reflux. The mixture is heated at the boiling point under reflux for a further hour and cooled to room temperature and 150 ml of ether are added. The precipitate is filtered off with suction and dissolved in 50 ml of ice-water and the solution is acidified to pH=6 with 10% strength hydrochloric acid. The precipitate is filtered off cold with suction, rinsed with ice-water and dried in vacuo at 40° C. 12 g of 2,4-dichlorobenzoylacetonitrile of melting point 96°-98° C. are obtained. under reflux The mixture is heated at the boiling point under reflux for a further hour The precipitate is filtered off with suction dissolved in 50 ml of ice-water The precipitate is filtered off cold with suction rinsed with ice-water dried in vacuo at 40° C

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of acetonitrile (2.0 mL, 38.2 mmol) in THF (50 mL) at −78° C. was added nBuLi (1.81 M in hexane, 16 mL, 28.7 mmol). The resulting slurry was kept at −78° C. for 15 min and 2,4-dichlorobenzoyl chloride (2.0 g, 9.55 mmol) was added dropwise to the acetonitrile anion. After 40 min, the reaction was quenched by addition of saturated NH4Cl (30 mL). THF was removed under reduced pressure and the suspension was filtered. The solid was washed with H2O (100 mL) and dried to give 3-(2,4-dichlorophenyl)-3-oxopropanenitrile (2.0 g, 98%, >95% purity) as a light yellow solid. After 40 min the reaction was quenched by addition of saturated NH4Cl (30 mL) THF was removed under reduced pressure the suspension was filtered The solid was washed with H2O (100 mL) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of acetonitrile (2.0 mL, 38.2 mmol) in THF (50 mL) at −78° C. was added nBuLi (1.81 M in hexane, 16 mL, 28.7 mmol). The resulting slurry was kept at −78° C. for 15 min and 2,4-dichlorobenzoyl chloride (2.0 g, 9.55 mmol) was added dropwise to the acetonitrile anion. After 40 min, the reaction was quenched by addition of saturated NH4Cl (30 mL). THF was removed under reduced pressure and the suspension was filtered. The solid was washed with H2O (100 mL) and dried to give 3-(2,4-dichlorophenyl)-3-oxopropanenitrile (2.0 g, 98%, >95% purity) as a light yellow solid. After 40 min the reaction was quenched by addition of saturated NH4Cl (30 mL) THF was removed under reduced pressure the suspension was filtered The solid was washed with H2O (100 mL) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 13.2 g. (0.056 mole) of 3,4-difluorophenacyl bromide was dissolved in 100 ml. of ethanol and cooled to 5° C. in ice. A solution of 7.6 g. (0.16 mole) of sodium cyanide in 40 ml. of water was added dropwise over 0.5 hr. and the reaction is stirred for an additional one hour. At that time, the mixture was diluted with 100 ml. of water and filtered through Celite®. Acidification of the filtrate gave a cloudy mixture which was extracted with methylene chloride. The organic phase was dried, filtered through Magnesol® and evaporated. Recrystallization of the residue from carbon tetrachloride provides 5.3 g. (52%) of colorless solid, m.p. 74°-75° C. Similarly prepared were 2,4-dichlorobenzoylacetonitrile, o-ethylbenzoylacetonitrile, p-isopropylbenzoylacetonitrile, m-isobutylbenzoylacetonitrile, 3,4-dimethylbenzoylacetonitrile, m-ethoxybenzoylacetonitrile, p-isopropoxybenzoylacetonitrile, 3,4-diethoxybenzoylacetonitrile, and 2,5-difluorobenzoylacetonitrile. At that time, the mixture was diluted with 100 ml of water and filtered through Celite® Acidification of the filtrate gave a cloudy mixture which was extracted with methylene chloride The organic phase was dried filtered through Magnesol® evaporated Recrystallization of the residue from carbon tetrachloride provides 5.3 g Similarly prepared

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 13.2 g. (0.056 mole) of 3,4-difluorophenacyl bromide was dissolved in 100 ml. of ethanol and cooled to 5° C. in ice. A solution of 7.6 g. (0.16 mole) of sodium cyanide in 40 ml. of water was added dropwise over 0.5 hr. and the reaction is stirred for an additional one hour. At that time, the mixture was diluted with 100 ml. of water and filtered through Celite®. Acidification of the filtrate gave a cloudy mixture which was extracted with methylene chloride. The organic phase was dried, filtered through Magnesol® and evaporated. Recrystallization of the residue from carbon tetrachloride provides 5.3 g. (52%) of colorless solid, m.p. 74°-75° C. Similarly prepared were 2,4-dichlorobenzoylacetonitrile, o-ethylbenzoylacetonitrile, p-isopropylbenzoylacetonitrile, m-isobutylbenzoylacetonitrile, 3,4-dimethylbenzoylacetonitrile, m-ethoxybenzoylacetonitrile, p-isopropoxybenzoylacetonitrile, 3,4-diethoxybenzoylacetonitrile, and 2,5-difluorobenzoylacetonitrile. At that time, the mixture was diluted with 100 ml of water and filtered through Celite® Acidification of the filtrate gave a cloudy mixture which was extracted with methylene chloride The organic phase was dried filtered through Magnesol® evaporated Recrystallization of the residue from carbon tetrachloride provides 5.3 g Similarly prepared

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: beta-Cyclodextrin (4.29 g, 3.78 mmol) was dissolved in water (75 mL) at 50° C. and a solution of 3-(2,4-dichlorophenyl)-3-oxopropanenitrile (810 mg, 3.8 mmol) in Acetone (3.80 mL) was added dropwise, followed by NBS (0.808 g, 4.54 mmol) and thiourea (0.346 g, 4.54 mmol). Reaction mixture was stirred at 50° C. 1 hr. LCMS indicated complete conversion. Reaction mixture was cooled to rt, extracted with ethyl acetate (3×50 mL), dried with MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO with 5-30% ethyl acetate in hexanes to give 0.43 g of the title compound (42%). LCMS: (FA) ES+, 270, 272. 1H NMR (400 MHz, d1-chloroform) δ 7.49 (d, J=1.84 Hz, 1H), 7.41 (d, J=8.30 Hz, 1H), 7.31 (dd, J=8.16, 1.74 Hz, 1H). Reaction mixture 1 hr Reaction mixture was cooled to rt extracted with ethyl acetate (3×50 mL) dried with MgSO4 filtered concentrated under reduced pressure The residue was purified by ISCO with 5-30% ethyl acetate in hexanes

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: beta-Cyclodextrin (4.29 g, 3.78 mmol) was dissolved in water (75 mL) at 50° C. and a solution of 3-(2,4-dichlorophenyl)-3-oxopropanenitrile (810 mg, 3.8 mmol) in Acetone (3.80 mL) was added dropwise, followed by NBS (0.808 g, 4.54 mmol) and thiourea (0.346 g, 4.54 mmol). Reaction mixture was stirred at 50° C. 1 hr. LCMS indicated complete conversion. Reaction mixture was cooled to rt, extracted with ethyl acetate (3×50 mL), dried with MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO with 5-30% ethyl acetate in hexanes to give 0.43 g of the title compound (42%). LCMS: (FA) ES+, 270, 272. 1H NMR (400 MHz, d1-chloroform) δ 7.49 (d, J=1.84 Hz, 1H), 7.41 (d, J=8.30 Hz, 1H), 7.31 (dd, J=8.16, 1.74 Hz, 1H). Reaction mixture 1 hr Reaction mixture was cooled to rt extracted with ethyl acetate (3×50 mL) dried with MgSO4 filtered concentrated under reduced pressure The residue was purified by ISCO with 5-30% ethyl acetate in hexanes

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: beta-Cyclodextrin (4.29 g, 3.78 mmol) was dissolved in water (75 mL) at 50° C. and a solution of 3-(2,4-dichlorophenyl)-3-oxopropanenitrile (810 mg, 3.8 mmol) in Acetone (3.80 mL) was added dropwise, followed by NBS (0.808 g, 4.54 mmol) and thiourea (0.346 g, 4.54 mmol). Reaction mixture was stirred at 50° C. 1 hr. LCMS indicated complete conversion. Reaction mixture was cooled to rt, extracted with ethyl acetate (3×50 mL), dried with MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO with 5-30% ethyl acetate in hexanes to give 0.43 g of the title compound (42%). LCMS: (FA) ES+, 270, 272. 1H NMR (400 MHz, d1-chloroform) δ 7.49 (d, J=1.84 Hz, 1H), 7.41 (d, J=8.30 Hz, 1H), 7.31 (dd, J=8.16, 1.74 Hz, 1H). Reaction mixture 1 hr Reaction mixture was cooled to rt extracted with ethyl acetate (3×50 mL) dried with MgSO4 filtered concentrated under reduced pressure The residue was purified by ISCO with 5-30% ethyl acetate in hexanes

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 8.8 g of 2,4-dichloro-benzoylacetonitrile, 69.2 g of methyl o-formate and 10.5 g of acetic anhydride is refluxed at a bath temperature of 150° C. for 3 hours. The volatile constituents are then distilled off in vacuo and finally under a fine vacuum at a bath temperature of 120° C. 11 g of 2-(2,4-dichloro-benzoyl)-3-methoxy-acrylonitrile are obtained as a viscous oil. The volatile constituents are then distilled off in vacuo and finally under a fine vacuum at a bath temperature of 120° C

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 8.8 g of 2,4-dichloro-benzoylacetonitrile, 69.2 g of methyl o-formate and 10.5 g of acetic anhydride is refluxed at a bath temperature of 150° C. for 3 hours. The volatile constituents are then distilled off in vacuo and finally under a fine vacuum at a bath temperature of 120° C. 11 g of 2-(2,4-dichloro-benzoyl)-3-methoxy-acrylonitrile are obtained as a viscous oil. The volatile constituents are then distilled off in vacuo and finally under a fine vacuum at a bath temperature of 120° C