3,5-二氯苯乙腈

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred mixture of 4-Chloro-5-ethyl-2,6-dimethoxy-pyrimidine (1.42 g, 7 mmol) and (3,5-Dichloro-phenyl)-acetonitrile (1.3 g, 7 mmol) in anhydrous DMF (14 ml) at 0° C. (ice bath) under nitrogen atmosphere, was portionwise added 60% sodium hydride (616 mg, 15.44 mmol). After stirring for 1 hr., the mixture was further stirred at room temperature for 18 hr. The mixture was then neutralized with aqueous saturated ammonium chloride solution and the crude product was extracted with ethyl acetate and purified by silica gel column chromatography (eluent, EA:hexanes (1:10)) to afford 2.1 g (85%) of the title compound as a white solid. m.p. 121-122° C.; 1H NMR (200 MHz, CDCl3) δ 1.03 (3H, t, J=7.4 Hz), 2.03-2.57 (2H, m), 3.98 (6H, s), 5.23 (1H, s), 7.33 (3H, s). , the mixture was further stirred at room temperature for 18 hr the crude product was extracted with ethyl acetate purified by silica gel column chromatography (eluent, EA:hexanes (1:10))

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred mixture of 4-Chloro-5-isopropyl-2,6-dimethoxy-pyrimidine (9.8 g, 45 mmol) and (3,5-Dichloro-phenyl)-acetonitrile (8.0 g, 43 mmol) in anhydrous DMF (70 ml) at 0° C. (ice bath) under nitrogen atmosphere, was portionwise added 60% sodium hydride (3.44 g, 86 mmol). After stirring for 1 hr., the mixture was further stirred at room temperature for overnight. The mixture was then neutralized with aqueous saturated ammonium chloride solution and the crude product was extracted with ethyl acetate and purified by silica gel column chromatography (eluent, EA:hexanes (1:9)) to afford 9.6 g (61%) of the title compound as a white solid. m.p. 135-136° C.; 1H NMR (200 MHz, CDCl3) δ 1.13 (3H, d, J=7.0 Hz), 1.18 (3H, d, J=7.0 Hz), 2.97 (1H, m), 3.99 (6H, s), 5.33 (1H, s), 7.25-7.33 (3H, m). , the mixture was further stirred at room temperature for overnight the crude product was extracted with ethyl acetate purified by silica gel column chromatography (eluent, EA:hexanes (1:9))

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The nitrile was added to a mixture of 40 mL of concentrated sulfuric acid and 50 mL H2O and heated to reflux for 48 hours, cooled to room temperature and stirred for 48 hours. The reaction was diluted into 1 L of crushed ice, warmed to room temperature and extracted with 2×200 mL of dichloromethane and 2×200 mL of ethylacetate. Both sets of organics were combined and washed with saturated aqueous NaHCO3. The NaHCO3 fractions were combined and acidified to pH 1 with 3N HCl. The white solid was too fine to filter and was extracted out with 2×200 mL of dichloromethane. The combined organics were dried with Na2SO4 and the solvents removed at reduced pressure to yield crude 3,5-dichlorophenylacetic acid as a white solid. The solid was slurried with hexane and filtered to get 1.75g of white solid. heated to reflux for 48 hours warmed to room temperature extracted with 2×200 mL of dichloromethane and 2×200 mL of ethylacetate washed with saturated aqueous NaHCO3 to filter was extracted out with 2×200 mL of dichloromethane The combined organics were dried with Na2SO4 the solvents removed at reduced pressure to yield crude 3,5-dichlorophenylacetic acid as a white solid filtered

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The nitrile was added to a mixture of 40 mL of concentrated sulfuric acid and 50 mL H2O and heated to reflux for 48 hours, cooled to room temperature and stirred for 48 hours. The reaction was diluted into 1 L of crushed ice, warmed to room temperature and extracted with 2×200 mL of dichloromethane and 2×200 mL of ethylacetate. Both sets of organics were combined and washed with saturated aqueous NaHCO3. The NaHCO3 fractions were combined and acidified to pH 1 with 3N HCl. The white solid was too fine to filter and was extracted out with 2×200 mL of dichloromethane. The combined organics were dried with Na2SO4 and the solvents removed at reduced pressure to yield crude 3,5-dichlorophenylacetic acid as a white solid. The solid was slurried with hexane and filtered to get 1.75 g of white solid. heated to reflux for 48 hours warmed to room temperature extracted with 2×200 mL of dichloromethane and 2×200 mL of ethylacetate washed with saturated aqueous NaHCO3 to filter was extracted out with 2×200 mL of dichloromethane The combined organics were dried with Na2SO4 the solvents removed at reduced pressure to yield crude 3,5-dichlorophenylacetic acid as a white solid filtered

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: This compound was prepared in a manner analogous to the compound of Example 6 from 3,5-dichlorophenylacetonitrile (Aldrich). mp. 242°-244° C.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of NaOEt (from 0.69 g sodium), in ethanol (25 ml) at reflux, was added over 5 minutes a mixture of 3,5-dichlorophenylacetonitrile (9.3 g) and ethyl acetate (3.3 g) in dry dimethoxyethane (10 ml). After stirring at reflux for 4 hours, the mixture was cooled on ice, acidified with acetic acid, poured into cold water and extracted with dichloromethane. The combined extracts were washed with water and concentrated to give an oil. Trituration with hexane gave 2-(3,5-dichlorophenyl)-3-oxobutyronitrile as a colourless solid (4.15 g). was added over 5 minutes at reflux for 4 hours the mixture was cooled on ice extracted with dichloromethane The combined extracts were washed with water concentrated to give an oil

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a vigorously stirred solution of 3,5-dichlorobenzylchloride (28 g) in dichloromethane (150 ml) was added a mixture of KCN (27.5 g) and tetrabutylammonium hydrogen sulphate (2.38 g) in water (110 ml). After stirring at room temperature for 22 hours, the mixture was diluted with dichloromethane, the organic phase washed with water and concentrated in vacuo to leave an oil. Filtration through silica with toluene followed by concentration then trituration with hexane gave the desired product as a colourless solid. 15.8 g, mp. 31°-32° C. the organic phase washed with water concentrated in vacuo to leave an oil Filtration through silica with toluene followed by concentration

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: This compound was prepared in a manner analogous to the compound of Example 6 from 3,5-dichlorophenylacetonitrile (Aldrich). mp. 242°-244° C.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of NaOEt (from 0.69 g sodium), in ethanol (25 ml) at reflux, was added over 5 minutes a mixture of 3,5-dichlorophenylacetonitrile (9.3 g) and ethyl acetate (3.3 g) in dry dimethoxyethane (10 ml). After stirring at reflux for 4 hours, the mixture was cooled on ice, acidified with acetic acid, poured into cold water and extracted with dichloromethane. The combined extracts were washed with water and concentrated to give an oil. Trituration with hexane gave 2-(3,5-dichlorophenyl)-3-oxobutyronitrile as a colourless solid (4.15 g). was added over 5 minutes at reflux for 4 hours the mixture was cooled on ice extracted with dichloromethane The combined extracts were washed with water concentrated to give an oil