methyl 3-fluorobenzoate

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

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

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

Procedure: To a stirred solution of dimethyl methylphosphonate (10.1 g, 81.2 mmol) in 100 ml of anhydrous THF was added dropwise n-butyl lithium (1.58N, 51.4 ml, 81.2 mmol) at -78° C. under argon atmosphere. After 30 minutes, methyl m-fluorobenzoate (5.0 g, 32 mmol) was further added dropwise and the mixture was stirred for 30 minutes. The reaction solution was allowed to warm to 0° C., diluted with 4.9 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue and the mixture was extracted with ethyl acetate (50 ml×2). The combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give an oil of dimethyl 2-m-fluorophenyl-2-oxo-ethylphosphonate (6.6 g, 26.8 mmol, yield 83.8%, b.p. 132°-134° C./0.17 mmHg), which was assigned the structure by the following data: concentrated 30 ml of water was added to the residue the mixture was extracted with ethyl acetate (50 ml×2) The combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1) dried over anhydrous sodium sulfate concentrated The residue was distilled under reduced pressure

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

Procedure: To an ice-cooled and stirred solution of m-fluorobenzoic acid (8.0 g, 57 mmol) in 50 ml of ether was added an excess solution of diazomethane in ether. After concentration, the residue was distilled under reduced pressure to give a colorless transparent oil of methyl m-fluorobenzoate (7.4 g, 48.1 mmol, yield 84.4%, b.p. 80°-82° C./16 mmHg), which was assigned the structure by the following data: After concentration the residue was distilled under reduced pressure

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

Procedure: To an ice-cooled and stirred solution of m-fluorobenzoic acid (8.0 g, 57 mmol) in 50 ml of ether was added an excess solution of diazomethane in ether. After concentration, the residue was distilled under reduced pressure to give a colorless transparent oil of methyl m-fluorobenzoate (7.4 g, 48.1 mmol, yield 84.4%, b.p. 80°-82° C./16 mmHg), which was assigned the structure by the following data: After concentration the residue was distilled under reduced pressure

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 ml, 4-necked flask fitted with a stirrer, thermometer, addition funnel and reflux condenser is charged sulfuric acid (50 ml) and methyl m-fluorobenzoate (8.5 g, 0.055 mole). The reaction mixture is then cooled to 5° C. and a solution of potassium nitrate (reagent 5.57 g, 0.055 mole) is concentrated sulfuric acid (50 ml) is added dropwise over a 30 minute period. Ten minutes after completion of addition the reaction mixture is poured onto 500 g of cracked ice and the product extracted into benzene (3×100 ml). The combined benzene extracts are dried with anhydrous magnesium sulfate and the filtrate reduced in vacuo to give 10.6 g (96%) of product, which is a yellow liquid. Anal. Calcd. for C8H6FNO4 : C, 48.20; H, 3.04; F, 9.54; N, 7.02. Found: C, 50.15; H, 3.34; F, 9.17; N, 6.77. To a 500 ml, 4-necked flask fitted with a stirrer thermometer, addition funnel reflux condenser is added dropwise over a 30 minute period Ten minutes after completion of addition the reaction mixture the product extracted into benzene (3×100 ml) The combined benzene extracts are dried with anhydrous magnesium sulfate

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

Procedure: To a 1-liter flask fitted with a stirrer, addition funnel, condenser, and drying tube containing diethyl ether (200 ml) and methanol (anhd.; 64 g,; 2.0 moles) is added dropwise m-fluorobenzoyl chloride (317 g,; 2.0 moles) at room temperature over a 3 hour period. Additional methanol (10 ml) is added and the reaction mixture is stirred at room temperature overnight. The reaction mixture is then filtered through a bed of silicic acid and the solvent removed under vacuum to afford 285 grams of methyl 3-fluorobenzoate (92.5% yield). This was identical to the product prepared in Example 2A. To a 1-liter flask fitted with a stirrer, addition funnel, condenser drying tube The reaction mixture is then filtered through a bed of silicic acid the solvent removed under vacuum

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

Procedure: To a solution of anhydrous hydrochloric acid (10.5 g) in anhydrous methanol (100 ml) is added m-fluorobenzoic acid (13.3 g.; 0.095 mole). The reaction mixture is stirred at room temperature overnight. The solvent and anhydrous hydrochloric acid are then removed under vacuum and the residue slurried with hexane (100 ml). The hexane insoluble layer is decanted and the hexane solution water washed (2×100 ml) before drying with anhydrous magnesium sulfate. The hexane filtrate is then concentrated under vacuum to afford 11.0 g (75% yield) of methyl 3-fluorobenzoate as a yellow liquid. Elemental anal. calcd. for C8H7FO2 : C, 62.35; H, 4.57; F, 12.33. Found: C, 62.52; H, 4.70; F, 11.89. The solvent and anhydrous hydrochloric acid are then removed under vacuum The hexane insoluble layer is decanted the hexane solution water washed (2×100 ml) before drying with anhydrous magnesium sulfate The hexane filtrate is then concentrated under vacuum

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

Procedure: To a solution of anhydrous hydrochloric acid (10.5 g) in anhydrous methanol (100 ml) is added m-fluorobenzoic acid (13.3 g.; 0.095 mole). The reaction mixture is stirred at room temperature overnight. The solvent and anhydrous hydrochloric acid are then removed under vacuum and the residue slurried with hexane (100 ml). The hexane insoluble layer is decanted and the hexane solution water washed (2×100 ml) before drying with anhydrous magnesium sulfate. The hexane filtrate is then concentrated under vacuum to afford 11.0 g (75% yield) of methyl 3-fluorobenzoate as a yellow liquid. Elemental anal. calcd. for C8H7FO2 : C, 62.35; H, 4.57; F, 12.33. Found: C, 62.52; H, 4.70; F, 11.89. The solvent and anhydrous hydrochloric acid are then removed under vacuum The hexane insoluble layer is decanted the hexane solution water washed (2×100 ml) before drying with anhydrous magnesium sulfate The hexane filtrate is then concentrated under vacuum

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 ml, 4-necked flask fitted with a stirrer, thermometer, addition funnel and reflux condenser is charged sulfuric acid (50 ml) and methyl m-fluorobenzoate (8.5 g, 0.055 mole). The reaction mixture is then cooled to 5° C. and a solution of potassium nitrate (reagent 5.57 g, 0.055 mole) is concentrated sulfuric acid (50 ml) is added dropwise over a 30 minute period. Ten minutes after completion of addition the reaction mixture is poured onto 500 g of cracked ice and the product extracted into benzene (3×100 ml). The combined benzene extracts are dried with anhydrous magnesium sulfate and the filtrate reduced in vacuo to give 10.6 g (96%) of product, which is a yellow liquid. Anal. Calcd. for C8H6FNO4 : C, 48.20; H, 3.04; F, 9.54; N, 7.02. Found: C, 50.15; H, 3.34; F, 9.17; N, 6.77. To a 500 ml, 4-necked flask fitted with a stirrer thermometer, addition funnel reflux condenser is added dropwise over a 30 minute period Ten minutes after completion of addition the reaction mixture the product extracted into benzene (3×100 ml) The combined benzene extracts are dried with anhydrous magnesium sulfate

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

Procedure: To a 1-liter flask fitted with a stirrer, addition funnel, condenser, and drying tube containing diethyl ether (200 ml) and methanol (anhd.; 64 g,; 2.0 moles] is added dropwise m-fluorobenzoyl chloride (317 g,; 2.0 moles) at room temperature over a 3 hour period. Additional methanol (10 ml) is added and the reaction mixture is stirred at room temperature overnight. The reaction mixture is then filtered through a bed of silicic acid and the solvent removed under vacuum to afford 285 grams of methyl 3-fluorobenzoate (92.5% yield). This was identical to the product prepared in Example 2A. To a 1-liter flask fitted with a stirrer, addition funnel, condenser drying tube containing diethyl ether (200 ml) and methanol (anhd The reaction mixture is then filtered through a bed of silicic acid the solvent removed under vacuum

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

Procedure: To a solution of anhydrous hydrochloric acid (10.5 g) in anhydrous methanol (100 ml) is added m-fluorobenzoic acid (13.3 g.; 0.095 mole). The reaction mixture is stirred at room temperature overnight. The solvent and anhydrous hydrochloric acid are then removed under vacuum and the residue slurried with hexane (100 ml). The hexane insoluble layer is decanted and the hexane solution water washed (2×100 ml) before drying with anhydrous magnesium sulfate. The hexane filtrate is then concentrated under vacuum to afford 11.0 g (75% yield) of methyl 3-fluorobenzoate as a yellow liquid. Elemental anal. calcd. for C8H7FO2 : C, 62.35; H, 4.57; F, 12.33. Found: C, 62.52; H, 4.70; F, 11.89. The solvent and anhydrous hydrochloric acid are then removed under vacuum The hexane insoluble layer is decanted the hexane solution water washed (2×100 ml) before drying with anhydrous magnesium sulfate The hexane filtrate is then concentrated under vacuum