2,3-dichloro-4-methoxybenzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 29.3 g of 2-bromopyridine in 150 ml of dry THF is added to 75 ml of 2.6M n-butyllithium that was chilled to -65° C. 2,3-dichloro-4-methoxybenzaldehyde (38.0 g) is then added in 300 ml of THF and the reaction mixture allowed to come to room temperature. It is poured into H2O and the crystalline product filtered off, washed with ether and dried to give α-(2,3-dichloro-4-methoxyphenyl)-2-pyridinemethanol, mp 174°-176° C. to come to room temperature the crystalline product filtered off washed with ether dried

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 29.3 g of 2-bromopyridine in 150 ml of dry THF is added to 75 ml of 2.6M n-butyllithium that was chilled to -65° C. 2,3-dichloro-4-methoxybenzaldehyde (38.0 g) is then added in 300 ml of THF and the reaction mixture allowed to come to room temperature. It is poured into H2O and the crystalline product filtered off, washed with ether and dried to give α-(2,3-dichloro-4-methoxyphenyl)-2-pyridinemethanol, mp 174°-176° C. to come to room temperature the crystalline product filtered off washed with ether dried

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 2,3-dichloro-4-methoxybenzaldehyde (158 gm., 0.77 mole), malonic acid (146 gm., 1.4 mole), pyridine (450 ml.) and piperidine (15 ml.) is heated and stirred on a steam bath for 23/4 hours. The hot reaction mixture is poured, with stirring into a mixture of concentrated hydrochloric acid (770 ml.) and crushed ice (3.1 kg.). is heated The hot reaction mixture is poured

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

実験手順: A mixture of 2,3-dichloro-4-hydroxybenzaldehyde (19.1 gm., ;b 0.1 mole) and potassium carbonate (34.4 gm., 0.25 mole) in dimethylformamide (50 ml.) is stirred and treated dropwise over 15 minutes with dimethyl sulfate (14.1 gm., 0.11 mole). The reaction is exothermic; after 45 minutes the mixture is poured with stirring into water (300 ml.). The solid product that separates is removed by filtration, washed with water and then washed with a little methanol. After drying the yield of 2,3-dichloro-4-methoxybenzaldehyde is 16 gm., m.p., 117°-118° C. after 45 minutes the mixture is poured The solid product that separates is removed by filtration washed with water washed with a little methanol After drying the yield of 2,3-dichloro-4-methoxybenzaldehyde m.p., 117°-118° C.

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

実験手順: A solution of 5.51 g of boron tribromide in methylene chloride is added dropwise to a solution of 2.05 g of 2,3-dichloro-4-methoxybenzaldehyde in methylene chloride. The mixture is stirred at room temperature for 4 hours, poured into ice-water and then extracted with ethyl acetate. The extract is washed with water, dried and evaporated to remove solvent. 10% hydrochloric acid and methanol are added to the residue and the mixture is stirred for 3 hours under ice-cooling and extracted with ethyl acetate again. The extract is washed with water, dried and evaporated to remove solvent. The residue is crystallized with isopropyl ether to give 1.82 g of 4-hydroxy-2,3-dichlorobenzaldehyde. extracted with ethyl acetate The extract is washed with water dried evaporated to remove solvent 10% hydrochloric acid and methanol are added to the residue the mixture is stirred for 3 hours under ice- cooling extracted with ethyl acetate again The extract is washed with water dried evaporated to remove solvent The residue is crystallized with isopropyl ether

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

実験手順: 4.13 ml of 1.6M n-butyl lithium in hexane are added dropwise to a tetrahydrfuran solution of 0.76 g of 1-ethoxymethylpyrazole at -60° C. under argon gas atmosphere. the mixture is stirred at -63° to -50° C. for 1 hour. A solution of 1.23 g of 2,3-dichloro-4-methoxybenzaldehyde in tetrahydrofuran is added to the mixture, and the mixture is stirred at -50° C. to room temperature for 1 hour. An aqueous saturated ammonium chloride solution and water are added to the mixture under ice-cooling and the mixture is concentrated to remove tetrahydrofuran. The residual aqueous layer is extracted with ethyl acetate and the extract is washed with water, dried and evaporated to give colorless crystals, which are then washed with isopropyl ether and dried to give 1.62 g of α-(1-ethoxymethyl-5-pyrazolyl)-2,3-dichloro-4-methoxy-benzylalcohol. the mixture is stirred at -50° C. to room temperature for 1 hour cooling the mixture is concentrated to remove tetrahydrofuran The residual aqueous layer is extracted with ethyl acetate the extract is washed with water dried evaporated to give colorless crystals, which are then washed with isopropyl ether dried

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

実験手順: The title compound was prepared by reacting 2,3-dichloro-4-methoxybenzaldehyde (10 g, 49 mmol) with boron tribromide (147 ml of 1N solution in CH2Cl2, 147 mmol) according to method D to yield 11.3 g dark grey solid which is mainly the designed product indicated by 1H-NMR. It was triturated with 30% CHCl3 in hexane to give 3.6 g of grey solid as pure product. An analytical sample was afforded as white solid by reverse-phase preparative HPLC: mp 176-178° C.; 1H NMR (DMSO-d6): δ 7.10 (1H, d, J=8.68 Hz), 7.74 (1H, d, J=8.67 Hz), 10.16 (1H, s), 11.95 (1H, s); MS (ESI) m/z 189/191/193 (M−H)−, 193/191/195 (M+H)+.

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

実験手順: A mixture of 2,3-dichloro-4-methoxybenzaldehyde (158 gm., 0.77 mole), malonic acid (146 gm., 1.4 mole), pyridine (450 ml.) and piperidine (15 ml.) is heated and stirred on a steam bath for 23/4 hours. The hot reaction mixture is poured, with stirring into a mixture of concentrated hydrochloric acid (770 ml.) and crushed ice (3.1 kg.). is heated The hot reaction mixture is poured

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 29.3 g of 2-bromopyridine in 150 ml of dry THF is added to 75 ml of 2.6M n-butyllithium that was chilled to -65° C. 2,3-dichloro-4-methoxybenzaldehyde (38.0 g) is then added in 300 ml of THF and the reaction mixture allowed to come to room temperature. It is poured into H2O and the crystalline product filtered off, washed with ether and dried to give α-(2,3-dichloro-4-methoxyphenyl)-2-pyridinemethanol, mp 174°-176° C. to come to room temperature the crystalline product filtered off washed with ether dried

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 29.3 g of 2-bromopyridine in 150 ml of dry THF is added to 75 ml of 2.6M n-butyllithium that was chilled to -65° C. 2,3-dichloro-4-methoxybenzaldehyde (38.0 g) is then added in 300 ml of THF and the reaction mixture allowed to come to room temperature. It is poured into H2O and the crystalline product filtered off, washed with ether and dried to give α-(2,3-dichloro-4-methoxyphenyl)-2-pyridinemethanol, mp 174°-176° C. to come to room temperature the crystalline product filtered off washed with ether dried