methyl 2-bromo-3-fluorobenzoate

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

Procedure: To a stirred solution of 4-iodo-1-trityl-1H-imidazole (436 mg, 1.0 mmol) in anhydrous THF (6 mL) was added EtMgBr (3.0 M in THF, 1.20 mmol, 0.40 mL) under an atmosphere of N2. The resulting solution was allowed to stir for 90 min and ZnCl2 (0.5 M in THF, 2.40 mL, 1.20 mmol) was added. The resulting white suspension was allowed to stir for 90 min and a solution of methyl 2-bromo-3-fluorobenzoate (280 mg, 1.20 mmol) in THF (1 mL) was added followed by the immediate addition of Pd(PPh3)4 (58 mg, 0.05 mmol). The reaction mixture was allowed to stir at 90° C. for 18 h under an atmosphere of N2. After cooling to room temperature, the solution was diluted with CH2Cl2 (20 mL) and the organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography to afford the desired product as yellow oil (190 mg, 41%). 1H NMR: 3.93 (s, 3H), 7.12-7.59 (m, 18H), 7.56 (s, 1H), 7.73-7.75 (m, 1H). to stir for 90 min to stir at 90° C. for 18 h under an atmosphere of N2 the organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine The organic layer was dried (Na2SO4) concentrated under reduced pressure The crude residue was purified by flash column chromatography

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

Procedure: To a suspension of 2-bromo-3-fluorobenzoic acid (300 mg, 1.37 mmol) in methanol (10 mL) at rt, was added SOCl2 (0.11 mL, 1.51 mmol) and the mixture was stirred at rt for 18 h. The solvent was distilled off under reduced pressure. The crude was basified by adding saturated aqueous NaHCO3 solution and the aqueous layer was extracted with EtOAc (3×25 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The obtained crude product was used in the next step without further purification. The solvent was distilled off under reduced pressure by adding saturated aqueous NaHCO3 solution the aqueous layer was extracted with EtOAc (3×25 mL) The combined organic layers were dried over Na2SO4 filtered concentrated The obtained crude product was used in the next step without further purification

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

Procedure: To a suspension of 2-bromo-3-fluorobenzoic acid (300 mg, 1.37 mmol) in methanol (10 mL) at rt, was added SOCl2 (0.11 mL, 1.51 mmol) and the mixture was stirred at rt for 18 h. The solvent was distilled off under reduced pressure. The crude was basified by adding saturated aqueous NaHCO3 solution and the aqueous layer was extracted with EtOAc (3×25 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The obtained crude product was used in the next step without further purification. The solvent was distilled off under reduced pressure by adding saturated aqueous NaHCO3 solution the aqueous layer was extracted with EtOAc (3×25 mL) The combined organic layers were dried over Na2SO4 filtered concentrated The obtained crude product was used in the next step without further purification

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

Procedure: To a stirred solution of 4-iodo-1-trityl-1H-imidazole (436 mg, 1.0 mmol) in anhydrous THF (6 mL) was added EtMgBr (3.0 M in THF, 1.20 mmol, 0.40 mL) under an atmosphere of N2. The resulting solution was allowed to stir for 90 min and ZnCl2 (0.5 M in THF, 2.40 mL, 1.20 mmol) was added. The resulting white suspension was allowed to stir for 90 min and a solution of methyl 2-bromo-3-fluorobenzoate (280 mg, 1.20 mmol) in THF (1 mL) was added followed by the immediate addition of Pd(PPh3)4 (58 mg, 0.05 mmol). The reaction mixture was allowed to stir at 90° C. for 18 h under an atmosphere of N2. After cooling to room temperature, the solution was diluted with CH2Cl2 (20 mL) and the organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography to afford the desired product as yellow oil (190 mg, 41%). 1H NMR: 3.93 (s, 3H), 7.12-7.59 (m, 18H), 7.56 (s, 1H), 7.73-7.75 (m, 1H). to stir for 90 min to stir at 90° C. for 18 h under an atmosphere of N2 the organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine The organic layer was dried (Na2SO4) concentrated under reduced pressure The crude residue was purified by flash column chromatography

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

Procedure: To a suspension of 2-bromo-3-fluorobenzoic acid (300 mg, 1.37 mmol) in methanol (10 mL) at rt, was added SOCl2 (0.11 mL, 1.51 mmol) and the mixture was stirred at rt for 18 h. The solvent was distilled off under reduced pressure. The crude was basified by adding saturated aqueous NaHCO3 solution and the aqueous layer was extracted with EtOAc (3×25 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The obtained crude product was used in the next step without further purification. The solvent was distilled off under reduced pressure by adding saturated aqueous NaHCO3 solution the aqueous layer was extracted with EtOAc (3×25 mL) The combined organic layers were dried over Na2SO4 filtered concentrated The obtained crude product was used in the next step without further purification

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

Procedure: To a stirred solution of 4-iodo-1-trityl-1H-imidazole (436 mg, 1.0 mmol) in anhydrous THF (6 mL) was added EtMgBr (3.0 M in THF, 1.20 mmol, 0.40 mL) under an atmosphere of N2. The resulting solution was allowed to stir for 90 min and ZnCl2 (0.5 M in THF, 2.40 mL, 1.20 mmol) was added. The resulting white suspension was allowed to stir for 90 min and a solution of methyl 2-bromo-3-fluorobenzoate (280 mg, 1.20 mmol) in THF (1 mL) was added followed by the immediate addition of Pd(PPh3)4 (58 mg, 0.05 mmol). The reaction mixture was allowed to stir at 90° C. for 18 h under an atmosphere of N2. After cooling to room temperature, the solution was diluted with CH2Cl2 (20 mL) and the organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography to afford the desired product as yellow oil (190 mg, 41%). 1H NMR: 3.93 (s, 3H), 7.12-7.59 (m, 18H), 7.56 (s, 1H), 7.73-7.75 (m, 1H). to stir for 90 min to stir at 90° C. for 18 h under an atmosphere of N2 the organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine The organic layer was dried (Na2SO4) concentrated under reduced pressure The crude residue was purified by flash column chromatography

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

Procedure: To a suspension of 2-bromo-3-fluorobenzoic acid (300 mg, 1.37 mmol) in methanol (10 mL) at rt, was added SOCl2 (0.11 mL, 1.51 mmol) and the mixture was stirred at rt for 18 h. The solvent was distilled off under reduced pressure. The crude was basified by adding saturated aqueous NaHCO3 solution and the aqueous layer was extracted with EtOAc (3×25 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The obtained crude product was used in the next step without further purification. The solvent was distilled off under reduced pressure by adding saturated aqueous NaHCO3 solution the aqueous layer was extracted with EtOAc (3×25 mL) The combined organic layers were dried over Na2SO4 filtered concentrated The obtained crude product was used in the next step without further purification