methyl 4-bromo-2-iodobenzoate

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

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and copper cyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the title compound (2.39 g). The reaction mixture was cooled the mixture was extracted with ethyl acetate The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine The organic layer was dried over sodium sulfate the solvent was evaporated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and copper cyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the title compound (2.39 g). The reaction mixture was cooled the mixture was extracted with ethyl acetate The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine The organic layer was dried over sodium sulfate the solvent was evaporated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and copper cyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the title compound (2.39 g). The reaction mixture was cooled the mixture was extracted with ethyl acetate The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine The organic layer was dried over sodium sulfate the solvent was evaporated

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

Procedure: To methyl 2-amino-4-bromobenzoate (5.75 g) was added cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07 g) was added by small portions under ice-cooling, and the mixture was stirred at the same temperature for 40 min. To this reaction mixture was added dropwise a solution of potassium iodide (8.3 g) in water (25 mL) under cooling to 5° C., 20% sulfuric acid (30 mL) was added, and the mixture was stirred at 5° C. for 2 hr. This reaction mixture was neutralized with 4N aqueous sodium hydroxide solution under ice-cooling, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (7.05 g). was added by small portions under ice- cooling the mixture was stirred at 5° C. for 2 hr cooling the mixture was extracted with ethyl acetate The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine dried over sodium sulfate the solvent was evaporated The obtained residue was purified by column chromatography (hexane:ethyl acetate)

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

Procedure: To methyl 2-amino-4-bromobenzoate (5.75 g) was added cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07 g) was added by small portions under ice-cooling, and the mixture was stirred at the same temperature for 40 min. To this reaction mixture was added dropwise a solution of potassium iodide (8.3 g) in water (25 mL) under cooling to 5° C., 20% sulfuric acid (30 mL) was added, and the mixture was stirred at 5° C. for 2 hr. This reaction mixture was neutralized with 4N aqueous sodium hydroxide solution under ice-cooling, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (7.05 g). was added by small portions under ice- cooling the mixture was stirred at 5° C. for 2 hr cooling the mixture was extracted with ethyl acetate The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine dried over sodium sulfate the solvent was evaporated The obtained residue was purified by column chromatography (hexane:ethyl acetate)

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

Procedure: To methyl 2-amino-4-bromobenzoate (5.75 g) was added cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07 g) was added by small portions under ice-cooling, and the mixture was stirred at the same temperature for 40 min. To this reaction mixture was added dropwise a solution of potassium iodide (8.3 g) in water (25 mL) under cooling to 5° C., 20% sulfuric acid (30 mL) was added, and the mixture was stirred at 5° C. for 2 hr. This reaction mixture was neutralized with 4N aqueous sodium hydroxide solution under ice-cooling, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (7.05 g). was added by small portions under ice- cooling the mixture was stirred at 5° C. for 2 hr cooling the mixture was extracted with ethyl acetate The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine dried over sodium sulfate the solvent was evaporated The obtained residue was purified by column chromatography (hexane:ethyl acetate)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 190 were added copper cyanide (1.16 g) and N-methylpyrrolidone (21 mL) and the mixture was stirred at 60° C. for 1 hr. Under cooling with water, ethyl acetate, saturated aqueous ammonium chloride solution and aqueous ammonia were added and the mixture was extracted with ethyl acetate. The organic layer was washed once with saturated aqueous ammonium chloride solution and aqueous ammonia, once with saturated aqueous ammonium chloride solution and once with saturated brine, and dried over sodium sulfate. The solvent was evaporated to give the title compound (2.39 g). were added the mixture was extracted with ethyl acetate The organic layer was washed once with saturated aqueous ammonium chloride solution and aqueous ammonia, once with saturated aqueous ammonium chloride solution and once with saturated brine dried over sodium sulfate The solvent was evaporated

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

Procedure: To methyl 2-amino-4-bromobenzoate (5.75 g) was added ice-cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07 g) was added by small portions under ice-cooling and the mixture was stirred for 40 min. To this reaction mixture was added dropwise a solution obtained by dissolving potassium iodide (8.3 g) in water (25 mL) under ice-cooling, 20% sulfuric acid (30 mL) was added and the mixture was stirred for 2 hr. This reaction mixture was neutralized with 4N aqueous sodium hydroxide solution under ice-cooling, and the mixture was extracted with ethyl acetate, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride. The organic layer was washed once with saturated brine and 10% aqueous sodium sulfite solution, with saturated brine, and dried over sodium sulfate. The solvent was evaporated and the residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (7.05 g). was added by small portions under ice- cooling To this reaction mixture was added dropwise a solution obtained cooling the mixture was stirred for 2 hr cooling the mixture was extracted with ethyl acetate, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride The organic layer was washed once with saturated brine and 10% aqueous sodium sulfite solution, with saturated brine dried over sodium sulfate The solvent was evaporated the residue was purified by column chromatography (hexane:ethyl acetate)