methyl 5-chloro-3-formyl-2-hydroxybenzoate

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3.0 g of methyl 5-chloro-3-formyl-2-hydroxybenzoate, 3.44 g of methyl α-bromophenylacetate, 8.28 g of potassium carbonate and 50 ml of dimethylformamide is heated at 70°-80° C. for 15 minutes and further heated at 100° C. for 10 minutes. After cooling, water is added to the mixture, and the aqueous mixture is acidified with 10% hydrochloric acid and then extracted with ethyl acetate. The extract is washed with an aqueous saturated sodium chloride solution, dried and evaporated to remove solvent. The residue is dissolved in 50 ml of ethanol, and 4.5 g of potassium hydroxide are added to the solution. The mixture is refluxed for 1 hour and then evaporated to remove solvent. Water is added to the residue, and the aqueous mixture is acidified with 10% hydrochloric acid and extracted with ethyl acetate. The extract is dried and evaporated to remove solvent. 150 ml of xylene and 30 mg of p-toluenesulfonic acid are added to the residue and the mixture is refluxed for 1 hour. The reaction mixture is evaporated to remove solvent and the residue is dissolved in ethyl acetate. The solution is washed, dried and evaporated to remove solvent. The residue is crystallized from isopropyl ether to give 2.32 g of 5-chloro-2-phenylbenzofuran-7-carboxylic acid. is heated at 70°-80° C. for 15 minutes After cooling extracted with ethyl acetate The extract is washed with an aqueous saturated sodium chloride solution dried evaporated to remove solvent The residue is dissolved in 50 ml of ethanol 4.5 g of potassium hydroxide are added to the solution The mixture is refluxed for 1 hour evaporated to remove solvent Water is added to the residue extracted with ethyl acetate The extract is dried evaporated to remove solvent 150 ml of xylene and 30 mg of p-toluenesulfonic acid are added to the residue the mixture is refluxed for 1 hour The reaction mixture is evaporated to remove solvent the residue is dissolved in ethyl acetate The solution is washed dried evaporated to remove solvent The residue is crystallized from isopropyl ether

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

Procedure: 193 g of 5-chloro-3-formyl-2-hydroxybenzoic acid are dissoved in 2 liters of methanol and the solution is saturated with hydrogen chloride. 100 ml of thionyl chloride are added to the solution and the mixture is refluxed for 8 hours. After cooling, the resultant crystals are collected by filtration and dried to give 190 g of methyl 5-chloro-3-formyl-2-hydroxybenzoate. the mixture is refluxed for 8 hours After cooling the resultant crystals are collected by filtration dried

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

Procedure: A solution of methyl 5-chloro-3-formyl-2-hydroxybenzoate (6.4 g, 30 mmol) in acetone (50 mL) was added with potassium carbonate (7.4 g, 54 mmol), the mixture was successively added with sodium iodide (0.60 g, 3.0 mmol) and methyl bromoacetate (6.9 g, 45 mmol), and the mixture was stirred at room temperature for 10 hours, and then refluxed for 5 hours by heating. The reaction mixture was cooled to room temperature, and then added with acetone, and the mixture was filtered through Celite. The solvent was evaporated from the filtrate under reduced pressure, the solid formed was suspended in hexane/ethyl acetate (9:1), thereby washed, and then collected by filtration to obtain the objective substance. The filtrate was concentrated under reduced pressure, and the residue was subjected to by silica gel column chromatography (eluted with hexane/ethyl acetate (9:1→1:1)) to further obtain the objective substance. Two portions of the objective substance were combined to obtain 6.5 g (75%) of methyl 5-chloro-3-formyl-2-(2-methoxy-2-oxoethoxy)benzoate. refluxed for 5 hours by heating The reaction mixture was cooled to room temperature the mixture was filtered through Celite The solvent was evaporated from the filtrate under reduced pressure the solid formed washed collected by filtration to obtain the objective substance The filtrate was concentrated under reduced pressure the residue was subjected to by silica gel column chromatography (eluted with hexane/ethyl acetate (9:1→1:1)) to further obtain the objective substance

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

Procedure: A mixture of methyl 5-chloro-3-formyl-2-hydroxybenzoate (73.2 g), ethylene glycol (350 ml) and trimethylchlorosilane (129 ml) is stirred at room temperature for 2 hours. The reaction mixture is poured into a mixture of an aqueous saturated sodium bicarbonate solution and trimethylamine, and the mixture is extracted with ethyl acetate. The extracted is washed with water, dried and concentrated to remove solvent, whereby methyl 5-chloro-3-(1,3-dioxolan-2-yl)-2-hydroxybenzoate (86 g) is obtained as yellow powder. the mixture is extracted with ethyl acetate The extracted is washed with water dried concentrated to remove solvent