4-bromo-2,5-difluorobenzonitrile

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: A solution of cyanuric chloride (3.12 g, 16.94 mmol) and dry DMF (8.5 mL) was stirred for 30 min or until the formation of white solid. Disappearance of cyanuric chloride was confirmed by TLC. (E)-4-bromo-2,5-difluorobenzaldehyde oxime (4.0 g, 16.94 mmol) in DMF (26 mL) was added dropwise to the suspension and stirred for 1 h. The reaction mixture was diluted with water and extracted with hexanes. The organic extract was washed with water, washed with saturated brine solution, dried (Na2SO4), filtered, and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography (SiO2, eluting with 2-20% ethyl acetate in hexanes) to provide the title compound as a white solid (2.5 g, 68%): 1H NMR (400 MHz, CDCl3) δ 7.40 (dd, J=5.36, 7.10 Hz, 1H), 7.52 (dd, J=5.40, 7.66 Hz, 1H); EIMS m/z 218. extracted with hexanes The organic extract was washed with water washed with saturated brine solution dried (Na2SO4) filtered evaporated to dryness under reduced pressure The crude product was purified by flash chromatography (SiO2, eluting with 2-20% ethyl acetate in hexanes)

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

Procedure: A solution of cyanuric chloride (3.12 g, 16.94 mmol) and dry DMF (8.5 mL) was stirred for 30 min or until the formation of white solid. Disappearance of cyanuric chloride was confirmed by TLC. (E)-4-bromo-2,5-difluorobenzaldehyde oxime (4.0 g, 16.94 mmol) in DMF (26 mL) was added dropwise to the suspension and stirred for 1 h. The reaction mixture was diluted with water and extracted with hexanes. The organic extract was washed with water, washed with saturated brine solution, dried (Na2SO4), filtered, and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography (SiO2, eluting with 2-20% ethyl acetate in hexanes) to provide the title compound as a white solid (2.5 g, 68%): 1H NMR (400 MHz, CDCl3) δ 7.40 (dd, J=5.36, 7.10 Hz, 1H), 7.52 (dd, J=5.40, 7.66 Hz, 1H); EIMS m/z 218. extracted with hexanes The organic extract was washed with water washed with saturated brine solution dried (Na2SO4) filtered evaporated to dryness under reduced pressure The crude product was purified by flash chromatography (SiO2, eluting with 2-20% ethyl acetate in hexanes)

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: This was prepared by the method of Example 43(a) using 4-bromo-2,5-difluorobenzonitrile and (R)-α-(2-chloroethyl)benzenemethanol. This was prepared by the method of Example 43(a)

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

Procedure: 4-Bromo-2,5-difluorobenzaldehyde (1.82 g, 8.3 mmol) and hydroxylamine-O-sulphonic acid (1.1 eq., 1.03 g) in water (40 ml) were heated to 100° C. for 6 h, cooled and extracted with ethyl acetate. The organic layer was dried (sodium sulphate) and evaporated to give the title compound as a pale yellow solid (1.2 g). cooled extracted with ethyl acetate The organic layer was dried (sodium sulphate) evaporated

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

Procedure: A solution of cyanuric chloride (3.12 g, 16.94 mmol) and dry DMF (8.5 mL) was stirred for 30 min or until the formation of white solid. Disappearance of cyanuric chloride was confirmed by TLC. (E)-4-bromo-2,5-difluorobenzaldehyde oxime (4.0 g, 16.94 mmol) in DMF (26 mL) was added dropwise to the suspension and stirred for 1 h. The reaction mixture was diluted with water and extracted with hexanes. The organic extract was washed with water, washed with saturated brine solution, dried (Na2SO4), filtered, and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography (SiO2, eluting with 2-20% ethyl acetate in hexanes) to provide the title compound as a white solid (2.5 g, 68%): 1H NMR (400 MHz, CDCl3) δ 7.40 (dd, J=5.36, 7.10 Hz, 1H), 7.52 (dd, J=5.40, 7.66 Hz, 1H); EIMS m/z 218. extracted with hexanes The organic extract was washed with water washed with saturated brine solution dried (Na2SO4) filtered evaporated to dryness under reduced pressure The crude product was purified by flash chromatography (SiO2, eluting with 2-20% ethyl acetate in hexanes)