methyl 3-bromo-4-chlorobenzoate

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 3-bromo-4-chlorobenzoate (120 mg, 0.481 mmol) was added to hydrazine (23.12 mg, 0.721 mmol) in methanol (8 mL) and refluxed for 12 h at 70° C. Reaction was monitored by TLC. After completion of the reaction, the solvent was removed by vacuum and then compound was purified by column chromatography affording the title compound (30 mg). 1H NMR (400 MHz, CDCl3): δ 8.02 (d, 1H, J=1.6 Hz), 7.60 (dd, 1H, J=2.0 & 8.0 Hz), 7.52 (d, 1H, J=8.0 Hz), ESI-MS: 250.9 [M+H]+. Reaction After completion of the reaction the solvent was removed by vacuum compound was purified by column chromatography

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

Procedure: 3-Bromo-4-chlorobenzoic acid (200 mg, 0.849 mmol) was refluxed in the presence of concentrated sulfuric acid (5.49 mg, 0.042 mmol) in methanol (10 mL) at 70° C. for overnight. The reaction was monitored by TLC. After completion of the reaction, the solvent was removed by vacuum, and the compound was purified by column chromatography affording the title compound (130 mg). 1H NMR (400 MHz, CDCl3): δ 8.29 (d, 1H, J=2.0 Hz), 7.91 (dd, 1H, J=2.0 & 8.4 Hz), 7.52 (d, 1H, J=8.4 Hz), 3.92 (s, 3H). ESI-MS: 250.9 [M+H]+. After completion of the reaction the solvent was removed by vacuum the compound was purified by column chromatography

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

Procedure: To a suspension of 3-bromo-4-chloro-benzoic acid (10 g, 42.6 mmol) in MeOH (100 mL) cooled with ice bath, was added acetyl chloride (30.4 mL, 0.43 mol) dropwise. The mixture was then stirred at room temperature for 12 hrs and concentrated to yield 3-bromo-4-chloro-benzoic acid methyl ester as a yellow solid (10.6 g). NMR (CDCl3), 6, 8.28 (1H, s), 7.91 (1H, brs), 7.52 (1H, brs), 3.92 (3H, s). cooled with ice bath concentrated

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

Procedure: To a suspension of 3-bromo-4-chloro-benzoic acid (10 g, 42.6 mmol) in MeOH (100 mL) cooled with ice bath, was added acetyl chloride (30.4 mL, 0.43 mol) dropwise. The mixture was then stirred at room temperature for 12 hrs and concentrated to yield 3-bromo-4-chloro-benzoic acid methyl ester as a yellow solid (10.6 g). NMR (CDCl3), 6, 8.28 (1H, s), 7.91 (1H, brs), 7.52 (1H, brs), 3.92 (3H, s). cooled with ice bath concentrated

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

Procedure: To a suspension of 3-bromo-4-chloro-benzoic acid (10 g, 42.6 mmol) in MeOH (100 mL) cooled with ice bath, was added acetyl chloride (30.4 mL, 0.43 mol) dropwise. The mixture was then stirred at room temperature for 12 hrs and concentrated to yield 3-bromo-4-chloro-benzoic acid methyl ester as a yellow solid (10.6 g). NMR (CDCl3), δ, 8.28 (1H, s), 7.91 (1H, brs), 7.52 (1H, brs), 3.92 (3H, s). cooled with ice bath concentrated

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

Procedure: To a suspension of 3-bromo-4-chloro-benzoic acid (10 g, 42.6 mmol) in MeOH (100 mL) cooled with ice bath, was added acetyl chloride (30.4 mL, 0.43 mol) dropwise. The mixture was then stirred at room temperature for 12 hrs and concentrated to yield 3-bromo-4-chloro-benzoic acid methyl ester as a yellow solid (10.6 g). NMR (CDCl3), δ, 8.28 (1H, s), 7.91 (1H, brs), 7.52 (1H, brs), 3.92 (3H, s). cooled with ice bath concentrated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In an atmosphere of nitrogen, a mixture of methyl 3-bromo-4-chlorobenzoate, (2,6-dimethylphenyl)boronic acid, lithium chloride, sodium carbonate, water, ethanol, dimethoxyethane and tetrakis(triphenylphosphine)palladium was stirred at 90° C. for 15 hours, thereby obtaining methyl 6-chloro-2′,6′-dimethylbiphenyl-3-carboxylate. Lithium aluminum hydride was added under ice-cooling to a THF solution of the resulting methyl 6-chloro-2′,6′-dimethylbiphenyl-3-carboxylate, followed by warming up to room temperature and stirring for 2 hours to obtain (6-chloro-2′,6′-dimethylbiphenyl-3-yl)methanol. by warming up to room temperature stirring for 2 hours

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In an atmosphere of nitrogen, a mixture of methyl 3-bromo-4-chlorobenzoate, (2,6-dimethylphenyl)boronic acid, lithium chloride, sodium carbonate, water, ethanol, dimethoxyethane and tetrakis(triphenylphosphine)palladium was stirred at 90° C. for 15 hours, thereby obtaining methyl 6-chloro-2′,6′-dimethylbiphenyl-3-carboxylate. Lithium aluminum hydride was added under ice-cooling to a THF solution of the resulting methyl 6-chloro-2′,6′-dimethylbiphenyl-3-carboxylate, followed by warming up to room temperature and stirring for 2 hours to obtain (6-chloro-2′,6′-dimethylbiphenyl-3-yl)methanol. by warming up to room temperature stirring for 2 hours

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a round bottom flask containing 13.1 (1.75 g, 7.01 mmol), 2-fluoro-5-methoxyphenylboronic acid (2.0 g, 11.8 mmol), tetrakis(triphenylphosphine)palladium(0) (0.81 g, 0.70 mmol), and potassium carbonate (2.91 g, 21.0 mmol) was added a premixed 3:1 solution of toluene (18 mL) and DMF (6 mL, 7.01 mmol). The mixture was heated at 100° C. and monitored with TLC. After 17 hours, the reaction was cooled to room temperature then partitioned between EtOAc and water. The aqueous layer was further extracted with EtOAc (2×20 mL). The organic layers were combined, washed with brine, and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtering, and the organic phase was concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2 gel 60, eluted with 0 to 20% EtOAc in hexanes) to yield a colorless oil 13.2 (1.01 g, 49% yield.) 1H NMR (400 MHz, CDCl3) δ ppm 8.04 (1H, m), 8.02 (1H, m) 7.57 (1H, d, J=8.2 Hz), 7.09 (1H, t, J=9.0 Hz), 6.93 (1H, dt, J=9.0, 3.5 Hz), 6.82 (1H, dd, J=5.1, 3.1 Hz), 3.93 (3H, s), 3.83 (3H, s). was added the reaction was cooled to room temperature then partitioned between EtOAc and water The aqueous layer was further extracted with EtOAc (2×20 mL) washed with brine dried over anhydrous magnesium sulfate The magnesium sulfate was removed by filtering the organic phase was concentrated under reduced pressure The residue was purified by flash chromatography (SiO2 gel 60, eluted with 0 to 20% EtOAc in hexanes)

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

Procedure: To a round bottom flask containing 3-bromo-4-chlorobenzoic acid (5.0 g, 21.2 mmol) (commercially available from Aldrich, CAS No. 42860-10-6) was added a cold solution of MeOH (60 mL) and sulfuric acid (1.4 mL). The mixture was heated to 80° C. and monitored with TLC. After 17 hours, the reaction was cooled to room temperature and diluted with water. The aqueous phase was extracted with diethyl ether (3×50 mL), and the combined organic layers were dried over anhydrous magnesium sulfate. After filtration, the organic solvent was removed in vacuo to yield white solid 13.1 (5.0 g, 96% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.28 (1H, d, J=2.0 Hz), 7.93 (1H, m), 7.52 (1H, d, J=8.2 Hz), 3.93 (3H, s). the reaction was cooled to room temperature The aqueous phase was extracted with diethyl ether (3×50 mL) the combined organic layers were dried over anhydrous magnesium sulfate After filtration the organic solvent was removed in vacuo

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

Procedure: To a suspension of 3-bromo-4-chloro-benzoic acid (10 g, 42.6 mmol) in MeOH (100 mL) cooled with ice bath, was added acetyl chloride (30.4 mL, 0.43 mol) dropwise. The mixture was then stirred at room temperature for 12 hrs and concentrated to yield 3-bromo-4-chloro-benzoic acid methyl ester as a yellow solid (10.6 g). NMR (CDCl3), δ, 8.28 (1H, s), 7.91 (1H, brs), 7.52 (1H, brs), 3.92 (3H, s). cooled with ice bath concentrated