5-chloro-2-methoxybenzaldehyde

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-chloro-2-methoxybenzaldehyde (32.2 g), cyanoethyl acetate and triethylbenzyl ammonium chloride (8.6 g) was stirred at 80° C. for 7 hours. To the reaction solution, isopropyl alcohol (97 ml) was added, then the mixture was stirred under ice cooling for 1 hour. The precipitated crystals were collected by filtration and dried in vacuo to obtain the title compound in an amount of 42.7 g as crystals. the mixture was stirred under ice cooling for 1 hour The precipitated crystals were collected by filtration dried in vacuo

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

Procedure: To a solution of 2-methoxybenzaldehyde (2g) in acetone (20 ml), water (40 ml) and acetic acid (4 ml) were added. Under ice cooling, calcium hypochlorite (5.25 g) was added, and then the mixture was stirred at that temperature for 1 hour and at room temperature for 2 hours. The reaction solution was extracted with methyl tert-butyl ether (20 ml×2), and the organic layer was washed with an aqueous sodium thiosulfate solution, then dried over magnesium sulfate. The solvent was distilled off in vacuo and the obtained residue was purified by slurry in heptane. The precipitated crystals were collected by filtration and dried in vacuo to obtain the title compound in an amount of 2.2 g as a colorless crystal. The reaction solution was extracted with methyl tert-butyl ether (20 ml×2) the organic layer was washed with an aqueous sodium thiosulfate solution dried over magnesium sulfate The solvent was distilled off in vacuo the obtained residue was purified by slurry in heptane The precipitated crystals were collected by filtration dried in vacuo

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

Procedure: To a solution of 2-methoxybenzaldehyde (2g) in acetone (20 ml), water (40 ml) and acetic acid (4 ml) were added. Under ice cooling, calcium hypochlorite (5.25 g) was added, and then the mixture was stirred at that temperature for 1 hour and at room temperature for 2 hours. The reaction solution was extracted with methyl tert-butyl ether (20 ml×2), and the organic layer was washed with an aqueous sodium thiosulfate solution, then dried over magnesium sulfate. The solvent was distilled off in vacuo and the obtained residue was purified by slurry in heptane. The precipitated crystals were collected by filtration and dried in vacuo to obtain the title compound in an amount of 2.2 g as a colorless crystal. The reaction solution was extracted with methyl tert-butyl ether (20 ml×2) the organic layer was washed with an aqueous sodium thiosulfate solution dried over magnesium sulfate The solvent was distilled off in vacuo the obtained residue was purified by slurry in heptane The precipitated crystals were collected by filtration dried in vacuo

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

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2-methoxy-5-chlorobenzaldehyde (34.5 g, 0.202 mole) in bis-(2-hydroxyethyl)ether (225 ml) was added hydrazine hydrate (17.7 g, 0.353 mole) and the mixture heated on a 125° C. oil bath for 15 minutes. It was then cooled to 50° C. and powdered potassium hydroxide (15.5 g of 85%, 0.24 mole) added. The mixture was heated on a 165° C. oil bath for 30 minutes. After it had cooled to room temperature it was poured into water (600 ml) and the aqueous solution acidified by addition of 6N HCl. Carbon tetrachloride (4×100 ml) extractions of the acid solution, followed by washing the pooled extracts with brine (1×100 ml), drying (MgSO4) and concentration in vacuo gave a clear viscous oil which crystallized upon addition of a small volume of petroleum ether and chilling in an ice bath. The white crystals were filtered and dried in vacuo. Yield=24.7 g (78 %); m.p. 35°-37° C. It was then cooled to 50° C. The mixture was heated on a 165° C. oil bath for 30 minutes After it had cooled to room temperature it Carbon tetrachloride (4×100 ml) extractions of the acid solution by washing the pooled extracts with brine (1×100 ml) drying (MgSO4) and concentration in vacuo gave a clear viscous oil which crystallized upon addition of a small volume of petroleum ether chilling in an ice bath The white crystals were filtered dried in vacuo

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2-methoxy-5-chlorobenzaldehyde (34.5 g, 0.202 mole) in bis-(2-hydroxyethyl)ether (225 ml) was added hydrazine hydrate (17.7 g, 0.353 mole) and the mixture heated on a 125° C. oil bath for 15 minutes. It was then cooled to 50° C. and powdered potassium hydroxide (15.5 g of 85%, 0.24 mole) added. The mixture was heated on a 165° C. oil bath for 30 minutes. After it had cooled to room temperature it was poured into water (600 ml) and the aqueous solution acidified by addition of 6N HCl. Carbon tetrachloride (4×100 ml) extractions of the acid solution, followed by washing the pooled extracts with brine (1×100 ml), drying (MgSO4) and concentration in vacuo gave a clear viscous oil which crystallized upon addition of a small volume of petroleum ether and chilling in an ice bath. The white crystals were filtered and dried in vacuo. Yield=24.7 g (78 %); m.p. 35°-37° C. It was then cooled to 50° C. The mixture was heated on a 165° C. oil bath for 30 minutes After it had cooled to room temperature it Carbon tetrachloride (4×100 ml) extractions of the acid solution by washing the pooled extracts with brine (1×100 ml) drying (MgSO4) and concentration in vacuo gave a clear viscous oil which crystallized upon addition of a small volume of petroleum ether chilling in an ice bath The white crystals were filtered dried in vacuo

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

Procedure: 4.3 g of 5-chlorosalicylaldehyde, together with 7.8 g of methyl iodide and 5.7 g of potassium carbonate, in 100 ml of acetone are heated to reflux (1 hour). After filtration, the filtrate is concentrated. 4.6 g of the title compound are obtained as an oil. to reflux (1 hour) After filtration the filtrate is concentrated

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

Procedure: In a manner similar to the method described in Example 1b, 4-chloro-2-fluorophenylacetonitrile (2.8 g, 16.6 mmol) was reacted with 5-chloro-2-methoxybenzaldehyde (Matrix) (3.4 g, 19.9 mmol), methanolic solution (25 wt %) of sodium methoxide (4.17 mL, 18 mmol) in methanol (100 mL) at 50° C. for 3 h to give (Z)-2-(4-chloro-2-fluoro-phenyl)-3-(5-chloro-2-methoxy-phenyl)-acrylonitrile as a white solid (2.0 g, 37%).

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

Procedure: In water (100 ml) was dissolved sodium hydroxide (3.0 g), and to the solution was added acetone (80 ml) and then was added dropwise a solution of 5-chloro-2-methoxybenzaldehyde (11.8 g) in acetone (30 ml). The reaction solution was stirred at room temperature for 2 hours, and acetone was evaporated under reduced pressure. The residue was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine and concentrated under reduced pressure. The residue was purified with silica gel column chromatography to give 4-(5-chloro-2-methoxyphenyl)-3-buten-2-one (6.8 g). acetone was evaporated under reduced pressure The residue was extracted with ethyl acetate the organic layer was washed with water and saturated brine concentrated under reduced pressure The residue was purified with silica gel column chromatography

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

Procedure: A solution of 5-chloro-2-methoxy-benzaldehyde (prepared according to U.S. Pat. No. 4,602,035) (2.04 g, 12.0 mmol) in methanol (80 mL) was added to a stirred solution of sodium cyanide (0.90 g) and ammonium chloride (1.50 g) in aqueous ammonium hydroxide (33% solution, 30 mL) at 0° C. then warmed to room temperature for 18 hours. The mixture was evaporated to dryness, the residues partitioned between DCM and water, the organics separated, washed with brine and evaporated under vacuum to afford 2.21 g (94%) of 2-amino-2-(5-chloro-2-methoxyphenyl)acetonitrile as an orange oil. LCMS (ESI) m+H=197.2. The mixture was evaporated to dryness the residues partitioned between DCM and water the organics separated, washed with brine evaporated under vacuum

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-chloro-2-methoxybenzaldehyde (32.2 g), cyanoethyl acetate and triethylbenzyl ammonium chloride (8.6 g) was stirred at 80° C. for 7 hours. To the reaction solution, isopropyl alcohol (97 ml) was added, then the mixture was stirred under ice cooling for 1 hour. The precipitated crystals were collected by filtration and dried in vacuo to obtain the title compound in an amount of 42.7 g as crystals. the mixture was stirred under ice cooling for 1 hour The precipitated crystals were collected by filtration dried in vacuo