methyl 4-fluoro-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 suspension of LiAlH4 (94.6 mg, 2.49 mmol) in THF (3 ml) was added dropwise a solution of methyl 4-fluoro-2-methoxybenzoate obtained in Example 23-2) (273.3 mg, 1.48 mmol) in THF (3 ml). The mixture was stirred for 1 hour. To the mixture was added dropwise aqueous THF followed by water. The mixture was extracted three times with ethyl acetate and dried over MgSO4. The solvent was evaporated to give the crude title compound (310.8 mg; 83%). The mixture was extracted three times with ethyl acetate dried over MgSO4 The solvent was evaporated

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

Procedure: Methyl 2-methoxy-4-fluoro-benzoate (1.6 gr, 9.7 mmol), K2CO3 (1.3 gr, 9.7 mmol) and N-methyl piperazine (1.3 mL, 11.7 mmol) were heated at 100° C. in DMSO (5 mL) for 20 hours. Reaction mixture was diluted with DCM and washed with water. Organic phase was dried over sodium sulfate and evaporated to dryness. Column chromatography purification on silica gel using dichloromethane/methanol 95:5 as the eluant, afforded 1.7 g (yield 66%) of the title compound. Reaction mixture washed with water Organic phase was dried over sodium sulfate evaporated to dryness Column chromatography purification on silica gel

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

Procedure: Methyl 2-methoxy-4-fluoro-benzoate (1.6 gr, 9.7 mmol), K2CO3 (1.3 gr, 9.7 mmol) and N-methyl piperazine (1.3 mL, 11.7 mmol) were heated at 100° C. in DMSO (5 mL) for 20 hours. Reaction mixture was diluted with DCM and washed with water. Organic phase was dried over sodium sulfate and evaporated to dryness. Column chromatography purification on silica gel using dichloromethane/methanol 95:5 as the eluant, afforded 1.7 g (yield 66%) of the title compound. Reaction mixture washed with water Organic phase was dried over sodium sulfate evaporated to dryness Column chromatography purification on silica gel

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

Procedure: Methyl 2-methoxy-4-fluoro-benzoate (1.6 gr, 9.7 mmol), K2CO3 (1.3 gr, 9.7 mmol) and N-methyl piperazine (1.3 mL, 11.7 mmol) were heated at 100° C. in DMSO (5 mL) for 20 hours. Reaction mixture was diluted with DCM and washed with water. Organic phase was dried over sodium sulfate and evaporated to dryness. Column chromatography purification on silica gel using dichloromethane/methanol 95:5 as the eluant, afforded 1.7 g (yield 66%) of the title compound. Reaction mixture washed with water Organic phase was dried over sodium sulfate evaporated to dryness Column chromatography purification on silica gel

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

Procedure: To a solution of 4-fluoro-2-methoxybenzoic acid (1.7 g, 10 mmol) in methanol (100 mL) was added thionyl chloride (5.73 g, 48 mmol) at 0° C. The resultant mixture was stirred for 12 hours and then solvent was evaporated in vacuo. To the residue, saturated sodium bicarbonate aqueous solution (50 mL) was added and the mixture was extracted with ethyl acetate (100 mL×3). The organic phase was dried by sodium sulfate. The mixture was filtered and the filtrate was concentrated in vacuo to give methyl 4-fluoro-2-methoxybenzoate (1.3 g, 70%). solvent was evaporated in vacuo To the residue, saturated sodium bicarbonate aqueous solution (50 mL) was added the mixture was extracted with ethyl acetate (100 mL×3) The organic phase was dried by sodium sulfate The mixture was filtered the filtrate was concentrated in vacuo

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

Procedure: Methyl 2-methoxy-4-fluoro-benzoate (1.6 gr, 9.7 mmol), K2CO3 (1.3 gr, 9.7 mmol) and N-methyl piperazine (1.3 mL, 11.7 mmol) were heated at 100° C. in DMSO (5 mL) for 20 hours. Reaction mixture was diluted with DCM and washed with water. Organic phase was dried over sodium sulfate and evaporated to dryness. Column chromatography purification on silica gel using dichloromethane/methanol 95:5 as the eluant, afforded 1.7 g (yield 66%) of the title compound. Reaction mixture washed with water Organic phase was dried over sodium sulfate evaporated to dryness Column chromatography purification on silica gel

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

Procedure: Methyl 2-methoxy-4-fluoro-benzoate (1.6 gr, 9.7 mmol), K2CO3 (1.3 gr, 9.7 mmol) and N-methyl piperazine (1.3 mL, 11.7 mmol) were heated at 100° C. in DMSO (5 mL) for 20 hours. Reaction mixture was diluted with DCM and washed with water. Organic phase was dried over sodium sulfate and evaporated to dryness. Column chromatography purification on silica gel using dichloromethane/methanol 95:5 as the eluant, afforded 1.7 g (yield 66%) of the title compound. Reaction mixture washed with water Organic phase was dried over sodium sulfate evaporated to dryness Column chromatography purification on silica gel

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

Procedure: Methyl 2-methoxy-4-fluoro-benzoate (1.6 gr, 9.7 mmol), K2CO3 (1.3 gr, 9.7 mmol) and N-methyl piperazine (1.3 mL, 11.7 mmol) were heated at 100° C. in DMSO (5 mL) for 20 hours. Reaction mixture was diluted with DCM and washed with water. Organic phase was dried over sodium sulfate and evaporated to dryness. Column chromatography purification on silica gel using dichloromethane/methanol 95:5 as the eluant, afforded 1.7 g (yield 66%) of the title compound. Reaction mixture washed with water Organic phase was dried over sodium sulfate evaporated to dryness Column chromatography purification on silica gel

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

Procedure: Methyl 2-methoxy-4-fluoro-benzoate (1.6 gr, 9.7 mmol), K2CO3 (1.3 gr, 9.7 mmol) and N-methyl piperazine (1.3 mL, 11.7 mmol) were heated at 100° C. in DMSO (5 mL) for 20 hours. Reaction mixture was diluted with DCM and washed with water. Organic phase was dried over sodium sulfate and evaporated to dryness. Column chromatography purification on silica gel using dichloromethane/methanol 95:5 as the eluant, afforded 1.7 g (yield 66%) of the title compound. Reaction mixture washed with water Organic phase was dried over sodium sulfate evaporated to dryness Column chromatography purification on silica gel

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

Procedure: To a solution of methyl 4-fluoro-2-methoxybenzoate (1.84 g, 10 mmol) in N,N-dimethylformamide (100 mL) were added phenol (0.94 g, 10 mmol) and potassium carbonate (2.67 g, 20 mmol). The mixture was heated to 80° C. and stirred for 12 hours. The solvent was evaporated in vacuo and the residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=7:1) to give methyl 2-methoxy-4-phenoxybenzoate (2.1 g, 81%). The solvent was evaporated in vacuo the residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=7:1)

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-fluoro-2-methoxybenzoate (50 g, 271.50 mmol) in sulfuric acid (150 mL) was added a solution of potassium nitrate (35.6 g, 352.48 mmol) in sulfuric acid (30 mL) dropwise with stirring for 45 min at 0-25° C. in an ice/water bath. The reaction was then quenched by the addition of water/ice. The solids were collected by filtration to afford methyl 4-fluoro-2-methoxy-5-nitrobenzoate as a white solid (40.0 g, 64%). The reaction was then quenched by the addition of water/ice The solids were collected by filtration