3-bromo-2-fluorobenzoyl chloride

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

Procedure: A suspension of 3-bromo-2-fluorobenzoic acid (1.009 g, 4.61 mmol) in DCM (25 mL) was stirred at rt and treated with oxalyl chloride (2.016 mL, 23.04 mmol), followed by a drop of DMF, causing gas evolution to commence. After 2.5 h, the solution was heated to boiling for 1-2 min and allowed to cool to rt. After 3 h total, the solution was concentrated to provide 3-bromo-2-fluorobenzoyl chloride as a dark yellow liquid (1.078 g, 99%). A portion of this (200 mg, 0.842 mmol) was dissolved in THF (1.5 mL) and added to a solution of dimethylamine (2 M in methanol, 2.0 mL, 4.00 mmol) in THF (2 mL). The mixture was stirred at rt for 18 h, then was concentrated. The residue was dissolved in EtOAc, washed sequentially with 1 M hydrochloric acid, NaHCO3 (aq) and brine, and dried and concentrated to provide 3-bromo-2-fluoro-N,N-dimethylbenzamide as a light yellow oil (192 mg, 93%). 1H NMR (400 MHz, chloroform-d) δ 7.60 (ddd, J=8.1, 6.5, 1.6 Hz, 1H) 7.32 (ddd, J=7.6, 5.9, 1.6 Hz, 1H) 7.09 (td, J=7.8, 0.7 Hz, 1H) 3.14 (s, 3H) 2.93 (d, J=1.5 Hz, 3H). Mass spectrum m/z 246, 248 (M+H)+. the solution was heated to boiling for 1-2 min to cool to rt After 3 h total the solution was concentrated

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

Procedure: A suspension of 3-bromo-2-fluorobenzoic acid (1.009 g, 4.61 mmol) in DCM (25 mL) was stirred at rt and treated with oxalyl chloride (2.016 mL, 23.04 mmol), followed by a drop of DMF, causing gas evolution to commence. After 2.5 h, the solution was heated to boiling for 1-2 min and allowed to cool to rt. After 3 h total, the solution was concentrated to provide 3-bromo-2-fluorobenzoyl chloride as a dark yellow liquid (1.078 g, 99%). A portion of this (200 mg, 0.842 mmol) was dissolved in THF (1.5 mL) and added to a solution of dimethylamine (2 M in methanol, 2.0 mL, 4.00 mmol) in THF (2 mL). The mixture was stirred at rt for 18 h, then was concentrated. The residue was dissolved in EtOAc, washed sequentially with 1 M hydrochloric acid, NaHCO3 (aq) and brine, and dried and concentrated to provide 3-bromo-2-fluoro-N,N-dimethylbenzamide as a light yellow oil (192 mg, 93%). 1H NMR (400 MHz, chloroform-d) δ 7.60 (ddd, J=8.1, 6.5, 1.6 Hz, 1H) 7.32 (ddd, J=7.6, 5.9, 1.6 Hz, 1H) 7.09 (td, J=7.8, 0.7 Hz, 1H) 3.14 (s, 3H) 2.93 (d, J=1.5 Hz, 3H). Mass spectrum m/z 246, 248 (M+H)+. the solution was heated to boiling for 1-2 min to cool to rt After 3 h total the solution was concentrated

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

Procedure: A suspension of 3-bromo-2-fluorobenzoic acid (1.009 g, 4.61 mmol) in DCM (25 mL) was stirred at rt and treated with oxalyl chloride (2.016 mL, 23.04 mmol), followed by a drop of DMF, causing gas evolution to commence. After 2.5 h, the solution was heated to boiling for 1-2 min and allowed to cool to rt. After 3 h total, the solution was concentrated to provide 3-bromo-2-fluorobenzoyl chloride as a dark yellow liquid (1.078 g, 99%). A portion of this (200 mg, 0.842 mmol) was dissolved in THF (1.5 mL) and added to a solution of dimethylamine (2 M in methanol, 2.0 mL, 4.00 mmol) in THF (2 mL). The mixture was stirred at rt for 18 h, then was concentrated. The residue was dissolved in EtOAc, washed sequentially with 1 M hydrochloric acid, NaHCO3 (aq) and brine, and dried and concentrated to provide 3-bromo-2-fluoro-N,N-dimethylbenzamide as a light yellow oil (192 mg, 93%). 1H NMR (400 MHz, chloroform-d) δ 7.60 (ddd, J=8.1, 6.5, 1.6 Hz, 1H) 7.32 (ddd, J=7.6, 5.9, 1.6 Hz, 1H) 7.09 (td, J=7.8, 0.7 Hz, 1H) 3.14 (s, 3H) 2.93 (d, J=1.5 Hz, 3H). Mass spectrum m/z 246, 248 (M+H)+. the solution was heated to boiling for 1-2 min to cool to rt After 3 h total the solution was concentrated