(2-bromo-5-fluorophenyl)hydrazine

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

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

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

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 (2-bromo-5-fluorophenyl)hydrazine (2.15 g, 10.5 mmol) and concentrated HCl (1.2 mL) in water (30 mL) was added glyoxylic acid hydrate (1.06 g, 11.5 mmol). The resulting mixture was stirred at room temperature for 2 h. The precipitate that formed was collected by filtration, washed with water and dried at reduced pressure to afford the title compound as a yellow solid (2.67 g, 98% yield): 1H NMR (400 MHz, DMSO-D6) δ ppm 12.57 (1H, s), 10.65 (1H, s), 7.65 (1H, s), 7.56 (1H, dd, J=8.7, 5.9 Hz), 7.31 (1H, dd, J=11.4, 3.0 Hz), 6.73 (1H, td, J=8.5, 3.0 Hz); LCMS (+ESI, M+H+) m/z 261-263. The precipitate that formed was collected by filtration washed with water dried at reduced pressure

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

Procedure: To a suspension of (2-bromo-5-fluoro-phenyl)-hydrazine hydrochloride (41 g, 0.17 mol; prepared from 2-bromo-5-fluoroaniline by the method described in U.S. Pat. No. 3,959,309 (1976) p-23, and p-48) in water (300 mL) and CH2Cl2 (200 mL) was added 1N—NaOH (200 mL) until the solution was basic. The CH2Cl2 layer was separated and the aqueous portion was further extracted with CH2Cl2 (150 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated to obtain 33 g (0.16 mol) of the title compound as an off-white powder: HPLC: 0.89 min (AP 97% at 220 nm); 1H NMR (CDCl3, 500 MHz) δ ppm 3.62 (2H, s, NH2), 5.75 (1H, s, NH), 6.37 (1H, m, 5-CH), 6.87 (1H, dd, J=11, 3 Hz, 3-CH), 7.31 (1H, dd, J=8.6, 5.8 Hz, 6-CH); 13C NMR (CDCl3, 125.8 Hz) 8 ppm 100.0 (d, J=29 Hz, 3-CH), 101.4 (d, J=2.9 Hz, 1-C), 106.1 (d, J=23 Hz, 5-CH), 133.1 (d, J=9.6 Hz, 6-CH), 149.1 (d, J=10.6 Hz, 2-C), 163.5 (d, J=244 Hz, 4-CF); LC/MS m/z 205/207 (M+H). The CH2Cl2 layer was separated the aqueous portion was further extracted with CH2Cl2 (150 mL) The combined organic extracts were dried (MgSO4) filtered concentrated