3-bromo-5-chloro-2-fluoroaniline

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

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

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

Procedure: To a solution of 3-bromo-5-chloro-2-fluoroaniline (SM-5, step 3, 0.52 g, 2.3 mmol) in pyridine (2.5 mL) cooled in an ice water bath was added propane-1-sulfonyl chloride (0.3 mL, 2.8 mmol). After 4 hours the solution was concentrated and partitioned between EtOAc (75 mL) and aqueous 0.1 M HCl solution (30 mL). The layers were separated and the organic phase was then washed with brine, dried (Na2SO4) and concentrated to give 778 mg of N-(3-bromo-5-chloro-2-fluorophenyl)propane-1-sulfonamide as a yellow solid which was carried forward without further purification: LCMS (m/z) not observed, tR=0.95 minute. After 4 hours the solution was concentrated partitioned between EtOAc (75 mL) and aqueous 0.1 M HCl solution (30 mL) The layers were separated the organic phase was then washed with brine dried (Na2SO4) concentrated

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

Procedure: tert-Butyl 3-bromo-5-chloro-2-fluorophenylcarbamate (1.0 g, 3.1 mmol) was treated with 4.0 M HCl in dioxane (10 mL) and the resulting reaction was maintained at room temperature for 4 hours. The reaction mixture was concentrated and partitioned between EtOAc (200 mL) and saturated aqueous NaHCO3 solution (75 mL). The layers were separated and the organic portion was washed with brine (75 mL), dried (Na2SO4), and concentrated to give 3-bromo-5-chloro-2-fluoroaniline as a colorless oil which was carried forward without further purification: LCMS (m/z) 225.9 (MH+), tR=0.96 minute; 1H NMR (400 MHz, CDCl3) δ 6.88 (m, 1H), 6.70 (d, J=7.0 Hz, 1H). the resulting reaction The reaction mixture was concentrated partitioned between EtOAc (200 mL) and saturated aqueous NaHCO3 solution (75 mL) The layers were separated the organic portion was washed with brine (75 mL) dried (Na2SO4) concentrated

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

Procedure: To a solution of 3-bromo-5-chloro-2-fluoroaniline (SM-5, step 3, 0.52 g, 2.3 mmol) in pyridine (2.5 mL) cooled in an ice water bath was added propane-1-sulfonyl chloride (0.3 mL, 2.8 mmol). After 4 hours the solution was concentrated and partitioned between EtOAc (75 mL) and aqueous 0.1 M HCl solution (30 mL). The layers were separated and the organic phase was then washed with brine, dried (Na2SO4) and concentrated to give 778 mg of N-(3-bromo-5-chloro-2-fluorophenyl)propane-1-sulfonamide as a yellow solid which was carried forward without further purification: LCMS(m/z) not observed, tR=0.95 minute. After 4 hours the solution was concentrated partitioned between EtOAc (75 mL) and aqueous 0.1 M HCl solution (30 mL) The layers were separated the organic phase was then washed with brine dried (Na2SO4) concentrated

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

Procedure: tert-Butyl 3-bromo-5-chloro-2-fluorophenylcarbamate (1.0 g, 3.1 mmol) was treated with 4.0 M HCl in dioxane (10 mL) and the resulting reaction was maintained at room temperature for 4 hours. The reaction mixture was concentrated and partitioned between EtOAc (200 mL) and saturated aqueous NaHCO3 solution (75 mL). The layers were separated and the organic portion was washed with brine (75 mL), dried (Na2SO4), and concentrated to give 3-bromo-5-chloro-2-fluoroaniline as a colorless oil which was carried forward without further purification: LCMS(m/z) 225.9 (MH+), tR=0.96 minute; 1H NMR (400 MHz, CDCl3) δ 6.88 (m, 1H), 6.70 (d, J=7.0 Hz, 1H). the resulting reaction The reaction mixture was concentrated partitioned between EtOAc (200 mL) and saturated aqueous NaHCO3 solution (75 mL) The layers were separated the organic portion was washed with brine (75 mL) dried (Na2SO4) concentrated

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

Procedure: A solution of tert-butyl 3-bromo-5-chloro-2-fluorophenylcarbamate (900 mg, 2.78 mmol) in DCM/TFA (1:1, 20 mL) was stirred at rt for 1 h. The reaction mixture was concentrated, then the residue was taken up in ethyl acetate and washed with aqueous sodium bicarbonate and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to provide the crude title compound (736 mg). MS m/z 223.9 (M+1). The reaction mixture was concentrated washed with aqueous sodium bicarbonate and brine The organic layer was dried over sodium sulfate filtered concentrated

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

Procedure: A solution of tert-butyl 3-bromo-5-chloro-2-fluorophenylcarbamate (900 mg, 2.78 mmol) in DCM/TFA (1:1, 20 mL) was stirred at rt for 1 h. The reaction mixture was concentrated, then the residue was taken up in ethyl acetate and washed with aqueous sodium bicarbonate and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to provide the crude title compound (736 mg). MS m/z 223.9 (M+1). The reaction mixture was concentrated washed with aqueous sodium bicarbonate and brine The organic layer was dried over sodium sulfate filtered concentrated

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

Procedure: To a solution of 3-bromo-5-chloro-2-fluoroaniline (SM-5, step 3, 0.52 g, 2.3 mmol) in pyridine (2.5 mL) cooled in an ice water bath was added propane-1-sulfonyl chloride (0.3 mL, 2.8 mmol). After 4 hours the solution was concentrated and partitioned between EtOAc (75 mL) and aqueous 0.1 M HCl solution (30 mL). The layers were separated and the organic phase was then washed with brine, dried (Na2SO4) and concentrated to give 778 mg of N-(3-bromo-5-chloro-2-fluorophenyl)propane-1-sulfonamide as a yellow solid which was carried forward without further purification: LCMS (m/z) not observed, tR=0.95 minute. After 4 hours the solution was concentrated partitioned between EtOAc (75 mL) and aqueous 0.1 M HCl solution (30 mL) The layers were separated the organic phase was then washed with brine dried (Na2SO4) concentrated

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

Procedure: tert-Butyl 3-bromo-5-chloro-2-fluorophenylcarbamate (1.0 g, 3.1 mmol) was treated with 4.0 M HCl in dioxane (10 mL) and the resulting reaction was maintained at room temperature for 4 hours. The reaction mixture was concentrated and partitioned between EtOAc (200 mL) and saturated aqueous NaHCO3 solution (75 mL). The layers were separated and the organic portion was washed with brine (75 mL), dried (Na2SO4), and concentrated to give 3-bromo-5-chloro-2-fluoroaniline as a colorless oil which was carried forward without further purification: LCMS (m/z) 225.9 (MH+), tR=0.96 minute; 1H NMR (400 MHz, CDCl3) δ 6.88 (m, 1H), 6.70 (d, J=7.0 Hz, 1H). the resulting reaction The reaction mixture was concentrated partitioned between EtOAc (200 mL) and saturated aqueous NaHCO3 solution (75 mL) The layers were separated the organic portion was washed with brine (75 mL) dried (Na2SO4) concentrated

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

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

Procedure: To a solution of 3-bromo-5-chloro-2-fluoroaniline (SM-5, step 3, 0.52 g, 2.3 mmol) in pyridine (2.5 mL) cooled in an ice water bath was added propane-1-sulfonyl chloride (0.3 mL, 2.8 mmol). After 4 hours the solution was concentrated and partitioned between EtOAc (75 mL) and aqueous 0.1 M HCl solution (30 mL). The layers were separated and the organic phase was then washed with brine, dried (Na2SO4) and concentrated to give 778 mg of N-(3-bromo-5-chloro-2-fluorophenyl)propane-1-sulfonamide as a yellow solid which was carried forward without further purification: LCMS (m/z) not observed, tR=0.95 minute. After 4 hours the solution was concentrated partitioned between EtOAc (75 mL) and aqueous 0.1 M HCl solution (30 mL) The layers were separated the organic phase was then washed with brine dried (Na2SO4) concentrated