methyl 3-bromo-2-chlorobenzoate

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

Procedure: To a DMF solution (30 ml) containing 2.70 g of 3-bromo-2-chlorobenzoic acid were added 1.10 ml of methyl iodide and 2.38 g of potassium carbonate in order at room temperature, followed by 1 hour of stirring. The reaction liquid was mixed with water and then diluted with ethyl acetate. After a layer separation operation, the organic layer was washed with water and saturated brine in that order, dried with anhydrous magnesium sulfate and then concentrated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography using ethyl acetate-n-hexane (100:3) as the elution solvent to obtain 2.26 g (79%) of methyl 3-bromo-2-chlorobenzoate. FA: 250 The reaction liquid After a layer separation operation the organic layer was washed with water and saturated brine in that order dried with anhydrous magnesium sulfate concentrated under a reduced pressure The thus obtained residue was purified by a silica gel column chromatography

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

Procedure: To a DMF solution (30 ml) containing 2.70 g of 3-bromo-2-chlorobenzoic acid were added 1.10 ml of methyl iodide and 2.38 g of potassium carbonate in order at room temperature, followed by 1 hour of stirring. The reaction liquid was mixed with water and then diluted with ethyl acetate. After a layer separation operation, the organic layer was washed with water and saturated brine in that order, dried with anhydrous magnesium sulfate and then concentrated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography using ethyl acetate-n-hexane (100:3) as the elution solvent to obtain 2.26 g (79%) of methyl 3-bromo-2-chlorobenzoate. FA: 250 The reaction liquid After a layer separation operation the organic layer was washed with water and saturated brine in that order dried with anhydrous magnesium sulfate concentrated under a reduced pressure The thus obtained residue was purified by a silica gel column chromatography

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

Procedure: To a DMF solution (30 ml) containing 2.70 g of 3-bromo-2-chlorobenzoic acid were added 1.10 ml of methyl iodide and 2.38 g of potassium carbonate in order at room temperature, followed by 1 hour of stirring. The reaction liquid was mixed with water and then diluted with ethyl acetate. After a layer separation operation, the organic layer was washed with water and saturated brine in that order, dried with anhydrous magnesium sulfate and then concentrated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography using ethyl acetate-n-hexane (100:3) as the elution solvent to obtain 2.26 g (79%) of methyl 3-bromo-2-chlorobenzoate. FA: 250 The reaction liquid After a layer separation operation the organic layer was washed with water and saturated brine in that order dried with anhydrous magnesium sulfate concentrated under a reduced pressure The thus obtained residue was purified by a silica gel column chromatography

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

Procedure: To a DMF solution (30 ml) containing 2.70 g of 3-bromo-2-chlorobenzoic acid were added 1.10 ml of methyl iodide and 2.38 g of potassium carbonate in order at room temperature, followed by 1 hour of stirring. The reaction liquid was mixed with water and then diluted with ethyl acetate. After a layer separation operation, the organic layer was washed with water and saturated brine in that order, dried with anhydrous magnesium sulfate and then concentrated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography using ethyl acetate-n-hexane (100:3) as the elution solvent to obtain 2.26 g (79%) of methyl 3-bromo-2-chlorobenzoate. FA: 250 The reaction liquid After a layer separation operation the organic layer was washed with water and saturated brine in that order dried with anhydrous magnesium sulfate concentrated under a reduced pressure The thus obtained residue was purified by a silica gel column chromatography

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

Procedure: To a solution of methyl 3-bromo-2-chlorobenzoate (1.9 g, 7.6 mmol) in THF (30 mL) was added Super Hydride (23 mL, 23 mmol) at 0° C. The reaction was allowed to stir for 16 hours. TLC showed clean reaction. The reaction was diluted with EtOAc, washed with brine, dried over sodium sulfate, and purified by MPLC to furnish (3-bromo-2-chlorophenyl)methariol. LC-MS (IE, m/z): 205 [M-17]+; reaction washed with brine dried over sodium sulfate purified by MPLC

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

Procedure: To a solution of methyl 3-amino-2-chlorobenzoate (2.0 g, 11 mmol) in 48% HBr (10 mL) and water (20 mL) was added an aqueous solution of sodium nitrite (0.89 g, 13 mmol) at 0° C. The mixture was allowed to stir at 0° C. for 30 minutes before it was added into a suspension of copper(I) bromide (2.3 g, 16 mmol) in water (10 mL) and 48% HBr (5 mL) at 0° C. The reaction was allowed to warm to RT slowly, and then heated to 60° C. for 5 minutes. TLC and LC suggested good reaction. The product was extracted with DCM (100 mL×2). The extractions were combined, dried over sodium sulfate, adsorbed onto silica gel, and purified by MPLC to deliver methyl 3-bromo-2-chlorobenzoate. LC-MS (IE, m/z): 251 [M+1]+; to warm to RT slowly heated to 60° C. for 5 minutes reaction The product was extracted with DCM (100 mL×2) The extractions dried over sodium sulfate purified by MPLC

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

Procedure: To a solution of methyl 3-bromo-2-chlorobenzoate (1.9 g, 7.6 mmol) in THF (30 mL) was added Super Hydride (23 mL, 23 mmol) at 0° C. The reaction was allowed to stir for 16 hours. The reaction was diluted with EtOAc, washed with brine, dried over sodium sulfate, and purified by MPLC to provide (3-bromo-2-chlorophenyl)methanol. LC-MS (IE, m/z): 205 [M-17]+; washed with brine dried over sodium sulfate purified by MPLC

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

Procedure: To a solution of methyl 3-amino-2-chlorobenzoate (2.0 g, 11 mmol) in 48% HBr (10 mL) and water (20 mL) was added an aqueous solution of sodium nitrite (0.89 g, 13 mmol) at 0° C. The mixture was allowed to stir at 0° C. for 30 minutes before it was added into a suspension of copper(I) bromide (2.3 g, 16 mmol) in water (10 mL) and 48% HBr (5 mL) at 0° C. The reaction was allowed to warm to RT slowly, and then heated to 60° C. for 5 minutes. The product was extracted with DCM (100 mL X 2). The extractions were combined, dried over sodium sulfate, adsorbed onto silica gel, and purified by MPLC to provide methyl 3-bromo-2-chlorobenzoate. LC-MS (IE, m/z): 251 [M+1]+ to warm to RT slowly heated to 60° C. for 5 minutes The product was extracted with DCM (100 mL X 2) The extractions dried over sodium sulfate purified by MPLC

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

Procedure: To a solution of methyl 3-bromo-2-chlorobenzoate (1.9 g, 7.6 mmol) in THF (30 mL) was added Super Hydride (23 mL, 23 mmol) at 0° C. The reaction was allowed to stir for 16 hours. The reaction was diluted with EtOAc, washed with brine, dried over sodium sulfate, and purified by MPLC to provide (3-bromo-2-chlorophenyl)methanol. LC-MS (IE, m/z): 205 [M−17]+; washed with brine dried over sodium sulfate purified by MPLC

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

Procedure: To a solution of methyl 3-amino-2-chlorobenzoate (2.0 g, 11 mmol) in 48% HBr (10 mL) and water (20 mL) was added an aqueous solution of sodium nitrite (0.89 g, 13 mmol) at 0° C. The mixture was allowed to stir at 0° C. for 30 minutes before it was added into a suspension of copper(I) bromide (2.3 g, 16 mmol) in water (10 mL) and 48% HBr (5 mL) at 0° C. The reaction was allowed to warm to RT slowly, and then heated to 60° C. for 5 minutes. The product was extracted with DCM (100 mL×2). The extractions were combined, dried over sodium sulfate, adsorbed onto silica gel, and purified by MPLC to provide methyl 3-bromo-2-chlorobenzoate. LC-MS (IE, m/z): 251 [M+1]+ to warm to RT slowly heated to 60° C. for 5 minutes The product was extracted with DCM (100 mL×2) The extractions dried over sodium sulfate purified by MPLC

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

Procedure: To a DMF solution (30 ml) containing 2.70 g of 3-bromo-2-chlorobenzoic acid were added 1.10 ml of methyl iodide and 2.38 g of potassium carbonate in order at room temperature, followed by 1 hour of stirring. The reaction liquid was mixed with water and then diluted with ethyl acetate. After a layer separation operation, the organic layer was washed with water and saturated brine in that order, dried with anhydrous magnesium sulfate and then concentrated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography using ethyl acetate-n-hexane (100:3) as the elution solvent to obtain 2.26 g (79%) of methyl 3-bromo-2-chlorobenzoate. FA: 250 The reaction liquid After a layer separation operation the organic layer was washed with water and saturated brine in that order dried with anhydrous magnesium sulfate concentrated under a reduced pressure The thus obtained residue was purified by a silica gel column chromatography