methyl 5-chloro-2-methoxybenzoate

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

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

Procedure: To a stirred solution of methyl 5-chloro-2-methoxybenzoate (23.1 g, 0.115 mol) in dioxane (300 mL) was added 2.5N NaOH (230 mL). The resulting mixture was stirred at room temperature for 4 hours, concentrated, diluted with H2O, and acidified with 2N HCl. 19.70 g (91%) of the desired product was collected by filtration as a white solid. concentrated diluted with H2O 19.70 g (91%) of the desired product was collected by filtration as a white solid

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

Procedure: A mixture of 5-chlorosalicylic acid (20.0 g, 0.116 mol), potassium carbonate (40.3 g, 0.290 mol), and dimethyl sulfate (36.5 g, 0.290 mol) in acetone (300 mL) was heated at reflux for 18 hours. The mixture was cooled, concentrated, diluted with H2O, and extracted with ethyl acetate (3×150 mL). The extracts were washed with H2O and saturated NaCl, dried (MgSO4), and concentrated to give 23.10 g (99%) of product as a brown oil. was heated at reflux for 18 hours The mixture was cooled concentrated diluted with H2O extracted with ethyl acetate (3×150 mL) The extracts were washed with H2O and saturated NaCl dried (MgSO4) concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-chloro-2-methoxy-benzoic acid methyl ester (20 g, 9.97 mmol) in THF (100 mL) at 0° C. was added dropwise a solution of lithium aluminum hydride (210 mL, 210 mmol, 1M soln. in THF). The solution was then warmed to reflux for 2 hours. The reaction was cooled to 0° C. and carefully quenched by the addition of cold water. The mixture was filtered through celite and the filter cake was washed with diethyl ether. The filtrate was washed with saturated aqueous sodium hydrogen carbonate then dried over magnesium sulfate. Concentration in vacuo gave the title compound (17.2 g). The solution was then warmed to reflux for 2 hours carefully quenched by the addition of cold water The mixture was filtered through celite the filter cake was washed with diethyl ether The filtrate was washed with saturated aqueous sodium hydrogen carbonate then dried over magnesium sulfate Concentration in vacuo

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

Procedure: To a stirred solution of methyl 5-chloro-2-methoxybenzoate (23.1 g, 0.115 mol) in dioxane (300 mL) was added 2.5N NaOH (230 mL). The resulting mixture was stirred at room temperature for 4 hours, concentrated, diluted with H2O, and acidified with 2N HCl. 19.70 g (91%) of the desired product was collected by filtration as a white solid. concentrated diluted with H2O 19.70 g (91%) of the desired product was collected by filtration as a white solid

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

Procedure: A mixture of 5-chlorosalicylic acid (20.0 g, 0.116 mol), potassium carbonate (40.3 g, 0.290 mol), and dimethyl sulfate (36.5 g, 0.290 mol) in acetone (300 mL) was heated at reflux for 18 hours. The mixture was cooled, concentrated, diluted with H2O, and extracted with ethyl acetate (3×150 mL). The extracts were washed with H2O and saturated NaCl, dried (MgSO4), and concentrated to give 23.10 g (99%) of product as a brown oil. was heated at reflux for 18 hours The mixture was cooled concentrated diluted with H2O extracted with ethyl acetate (3×150 mL) The extracts were washed with H2O and saturated NaCl dried (MgSO4) concentrated

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

Procedure: A mixture of 5-chlorosalicylic acid (20.0 g, 0.116 mol), potassium carbonate (40.3 g, 0.290 mol), and dimethyl sulfate (36.5 g, 0.290 mol) in acetone (300 mL) was heated at reflux for 18 hours. The mixture was cooled, concentrated, diluted with H2O, and extracted with ethyl acetate (3×150 mL). The extracts were washed with H2O and saturated NaCl, dried (MgSO4), and concentrated to give 23.10 g (99%) of product as a brown oil. was heated at reflux for 18 hours The mixture was cooled concentrated diluted with H2O extracted with ethyl acetate (3×150 mL) The extracts were washed with H2O and saturated NaCl dried (MgSO4) concentrated

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

Procedure: To a solution of methyl 5-chloro-2-methoxybenzoate (25.4 g, 127 mmol) in ether (200 ml), cooled in an ice water bath, was added dropwise lithium tetrahydroaluminate (1 M in diethyl ether, 110 ml, 110 mmol). After 2 hours the reaction was quenched with water and then acidified to pH 3 with hydrochloric acid (6 M aqueous solution). The layers were separated and the organic layer dried over magnesium sulfate, filtered and concentrated in vacuo to give a white solid. The solid was dissolved dichloromethane (200 ml) and treated with thionyl chloride (25 ml, 340 mmol). After heating at reflux for 2 hours, the reaction was cooled to room temperature and water added. The layers were separated and the aqueous layer extracted with dichloromethane (2×50 ml). The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo to give an orange solid. This solid was dissolved dimethyl sulphoxide (175 ml), sodium cyanide (12.75 g, 260.2 mmol) added and solution heated to 80° C. for 3 hours. After cooling to room temperature, water was added and a solid formed that was filtered and washed with water to provide the title compound as an off white solid, 20.8 g, 91% yield. After 2 hours the reaction was quenched with water The layers were separated the organic layer dried over magnesium sulfate filtered concentrated in vacuo to give a white solid After heating at reflux for 2 hours The layers were separated the aqueous layer extracted with dichloromethane (2×50 ml) The combined organics were dried over magnesium sulfate filtered concentrated in vacuo to give an orange solid added solution heated to 80° C. for 3 hours After cooling to room temperature a solid formed that was filtered washed with water

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-chloro-2-methoxy-benzoic acid methyl ester (20 g, 9.97 mmol) in THF (100 mL) at 0° C. was added dropwise a solution of lithium aluminum hydride (210 mL, 210 mmol, 1M soln. in THF). The solution was then warmed to reflux for 2 hours. The reaction was cooled to 0° C. and carefully quenched by the addition of cold water. The mixture was filtered through celite and the filter cake was washed with diethyl ether. The filtrate was washed with saturated aqueous sodium hydrogen carbonate then dried over magnesium sulfate. Concentration in vacuo gave the title compound (17.2 g). The solution was then warmed to reflux for 2 hours carefully quenched by the addition of cold water The mixture was filtered through celite the filter cake was washed with diethyl ether The filtrate was washed with saturated aqueous sodium hydrogen carbonate then dried over magnesium sulfate Concentration in vacuo

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

Procedure: To a solution of methyl 5-chloro-2-methoxybenzoate (25.4 g, 127 mmol) in ether (200 ml), cooled in an ice water bath, was added dropwise lithium tetrahydroaluminate (1 M in diethyl ether, 110 ml, 110 mmol). After 2 hours the reaction was quenched with water and then acidified to pH 3 with hydrochloric acid (6 M aqueous solution). The layers were separated and the organic layer dried over magnesium sulfate, filtered and concentrated in vacuo to give a white solid. The solid was dissolved dichloromethane (200 ml) and treated with thionyl chloride (25 ml, 340 mmol). After heating at reflux for 2 hours, the reaction was cooled to room temperature and water added. The layers were separated and the aqueous layer extracted with dichloromethane (2×50 ml). The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo to give an orange solid. This solid was dissolved dimethyl sulphoxide (175 ml), sodium cyanide (12.75 g, 260.2 mmol) added and solution heated to 80° C. for 3 hours. After cooling to room temperature, water was added and a solid formed that was filtered and washed with water to provide the title compound as an off white solid, 20.8 g, 91% yield. After 2 hours the reaction was quenched with water The layers were separated the organic layer dried over magnesium sulfate filtered concentrated in vacuo to give a white solid After heating at reflux for 2 hours The layers were separated the aqueous layer extracted with dichloromethane (2×50 ml) The combined organics were dried over magnesium sulfate filtered concentrated in vacuo to give an orange solid added solution heated to 80° C. for 3 hours After cooling to room temperature a solid formed that was filtered washed with water

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-chloro-2-methoxy-benzoic acid methyl ester (20 g, 9.97 mmol) in THF (100 mL) at 0° C. was added dropwise a solution of lithium aluminum hydride (210 mL, 210 mmol, 1M soln. in THF). The solution was then warmed to reflux for 2 hours. The reaction was cooled to 0° C. and carefully quenched by the addition of cold water. The mixture was filtered through celite and the filter cake was washed with diethyl ether. The filtrate was washed with saturated aqueous sodium hydrogen carbonate then dried over magnesium sulfate. Concentration in vacuo gave the title compound (17.2 g). The solution was then warmed to reflux for 2 hours carefully quenched by the addition of cold water The mixture was filtered through celite the filter cake was washed with diethyl ether The filtrate was washed with saturated aqueous sodium hydrogen carbonate then dried over magnesium sulfate Concentration in vacuo

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