ethyl 2-chlorobenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4-chlorophenyl)acetonitrile (15.1 g, 100 mmol) in THF (250 ml) was added NaH (60% dispersion in oil, 8.0 g, 200 mmol) in 3 portions over 5 minutes. To this was added a solution of 2-chlorobenzoic acid ethyl ester (18.3 g, 100 mmol) in THF (50 ml), dropwise over 10 minutes. The mixture was then heated at 60° C. overnight. After cooling to room temperature, water was added (2×10 ml, bubbling observed), and the reaction was concentrated, in vacuo, to ½ volume. The mixture was diluted with water (125 ml) and methylene chloride (125 ml), adjusted to pH=7 with 3 N aqueous HCl, and the aqueous layer separated and extracted with additional methylene chloride. The combined organics were dried (MgSO4) and concentrated, in vacuo, to give a brown oil (33 g) that began to solidify on standing. After stirring the residue overnight in diisopropyl ether (250 ml), the solid product was collected by vacuum filtration to afford, after drying, in vacuo, title product I-3A-1a (15.2 g, 52%) as a tan solid: −ESI MS (M−1) 288.0; 1H NMR (400 MHz, CD2Cl2) δ 7.74 (d, J=8.30 Hz, 1H), 7.60–7.25 (m, 7H), 5.65 (s, 1H). After cooling to room temperature (2×10 ml, bubbling observed) the reaction was concentrated, in vacuo The mixture was diluted with water (125 ml) and methylene chloride (125 ml) the aqueous layer separated extracted with additional methylene chloride The combined organics were dried (MgSO4) concentrated, in vacuo

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4-chlorophenyl)acetonitrile (15.1 g, 100 mmol) in THF (250 ml) was added NaH (60% dispersion in oil, 8.0 g, 200 mmol) in 3 portions over 5 minutes. To this was added a solution of 2-chlorobenzoic acid ethyl ester (18.3 g, 100 mmol) in THF (50 ml), dropwise over 10 minutes. The mixture was then heated at 60° C. overnight. After cooling to room temperature, water was added (2×10 ml, bubbling observed), and the reaction was concentrated, in vacuo, to ½ volume. The mixture was diluted with water (125 ml) and methylene chloride (125 ml), adjusted to pH=7 with 3 N aqueous HCl, and the aqueous layer separated and extracted with additional methylene chloride. The combined organics were dried (MgSO4) and concentrated, in vacuo, to give a brown oil (33 g) that began to solidify on standing. After stirring the residue overnight in diisopropyl ether (250 ml), the solid product was collected by vacuum filtration to afford, after drying, in vacuo, title product I-3A-1a (15.2 g, 52%) as a tan solid: −ESI MS (M−1) 288.0; 1H NMR (400 MHz, CD2Cl2) δ 7.74 (d, J=8.30 Hz, 1H), 7.60–7.25 (m, 7H), 5.65 (s, 1H). After cooling to room temperature (2×10 ml, bubbling observed) the reaction was concentrated, in vacuo The mixture was diluted with water (125 ml) and methylene chloride (125 ml) the aqueous layer separated extracted with additional methylene chloride The combined organics were dried (MgSO4) concentrated, in vacuo

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4-chlorophenyl)acetonitrile (15.1 g, 100 mmol) in THF (250 ml) was added NaH (60% dispersion in oil, 8.0 g, 200 mmol) in 3 portions over 5 minutes. To this was added a solution of 2-chlorobenzoic acid ethyl ester (18.3 g, 100 mmol) in THF (50 ml), dropwise over 10 minutes. The mixture was then heated at 60° C. overnight. After cooling to room temperature, water was added (2×10 ml, bubbling observed), and the reaction was concentrated, in vacuo, to ½ volume. The mixture was diluted with water (125 ml) and methylene chloride (125 ml), adjusted to pH=7 with 3 N aqueous HCl, and the aqueous layer separated and extracted with additional methylene chloride. The combined organics were dried (MgSO4) and concentrated, in vacuo, to give a brown oil (33 g) that began to solidify on standing. After stirring the residue overnight in diisopropyl ether (250 ml), the solid product was collected by vacuum filtration to afford, after drying, in vacuo, title product I-3A-1a (15.2 g, 52%) as a tan solid: −ESI MS (M−1) 288.0; 1H NMR (400 MHz, CD2Cl2) δ 7.74 (d, J=8.30 Hz, 1H), 7.60–7.25 (m, 7H), 5.65 (s, 1H). After cooling to room temperature (2×10 ml, bubbling observed) the reaction was concentrated, in vacuo The mixture was diluted with water (125 ml) and methylene chloride (125 ml) the aqueous layer separated extracted with additional methylene chloride The combined organics were dried (MgSO4) concentrated, in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5 parts of 4-(1H-imidazol-1-ylmethyl)-1,2-benzenediamine, 5 parts of ethyl 2-chlorobenzoate and 30 parts of polyphosphoric acid was stirred for 4 hours at 140° C. The whole was poured into 200 parts of water and crushed ice. The mixture was treated with ammonium hydroxide. The product was extracted three times with 120 parts of trichloromethane. The combined extracts were dried, filtered and evaporated. The residue was purified by column chromatography (HPLC) over silica gel using a mixture of trichloromethane, methanol and ammonium hydroxide (90:10:0.05 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2-propanone and 1,1'-oxybisethane. The product was filtered off and dried in vacuo at 100° C., yielding 2.1 parts (26%) of 2-(2-chlorophenyl)-5-(1H-imidazol-1-ylmethyl)-1H-benzimidazole; mp. 115.2° C. (compound 88). crushed ice The product was extracted three times with 120 parts of trichloromethane The combined extracts were dried filtered evaporated The residue was purified by column chromatography (HPLC) over silica gel using a mixture of trichloromethane, methanol and ammonium hydroxide (90:10:0.05 by volume) as eluent The pure fractions were collected the eluent was evaporated The residue was crystallized from a mixture of 2-propanone and 1,1'-oxybisethane The product was filtered off dried in vacuo at 100° C.

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4-chlorophenyl)acetonitrile (15.1 g, 100 mmol) in THF (250 ml) was added NaH (60% dispersion in oil, 8.0 g, 200 mmol) in 3 portions over 5 minutes. To this was added a solution of 2-chlorobenzoic acid ethyl ester (18.3 g, 100 mmol) in THF (50 ml), dropwise over 10 minutes. The mixture was then heated at 60° C. overnight. After cooling to room temperature, water was added (2×10 ml, bubbling observed), and the reaction was concentrated, in vacuo, to ½ volume. The mixture was diluted with water (125 ml) and methylene chloride (125 ml), adjusted to pH=7 with 3 N aqueous HCl, and the aqueous layer separated and extracted with additional methylene chloride. The combined organics were dried (MgSO4) and concentrated, in vacuo, to give a brown oil (33 g) that began to solidify on standing. After stirring the residue overnight in diisopropyl ether (250 ml), the solid product was collected by vacuum filtration to afford, after drying, in vacuo, title product I-3A-1a (15.2 g, 52%) as a tan solid: −ESI MS (M−1) 288.0; 1H NMR (400 MHz, CD2Cl2) δ 7.74 (d, J=8.30 Hz, 1H), 7.60–7.25 (m, 7H), 5.65 (s, 1H). After cooling to room temperature (2×10 ml, bubbling observed) the reaction was concentrated, in vacuo The mixture was diluted with water (125 ml) and methylene chloride (125 ml) the aqueous layer separated extracted with additional methylene chloride The combined organics were dried (MgSO4) concentrated, in vacuo