2-bromo-4-fluoro-5-methoxyaniline

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

Procedure: To 6-bromo-4-fluoro-3-methoxyaniline (7.0 g, 32 mmol) was added conc. HCl (10 ml) followed by p-chloranil (7.80 g, 32 mmol), then nbutanol (10 ml) was added and the whole mix heated up to reflux, with stirring. A solution of crotonaldehyde (2.7 g 38.4 mmol) in nbutanol (5 ml), was added slowly over 0.5 h, and reflux continued for a further 0.5 h. The reaction mixture was allowed to cool, and the basified to pH14 using 50% NaOH solution. The reaction mixture was diluted with water (200 ml) and extracted with dichloromethane (3×100 ml). The combined organic extracts were dried over Na2SO4 and evaporated in vacuo to give a dark oil which was chromatographed on silica gel (˜200 g) eluting from 20% ethyl acetate in hexane to give the title compound as a brown oil (2.97 g, 34%). nbutanol (10 ml) was added the whole mix heated up to reflux reflux to cool extracted with dichloromethane (3×100 ml) The combined organic extracts were dried over Na2SO4 evaporated in vacuo to give a dark oil which was chromatographed on silica gel (˜200 g) eluting from 20% ethyl acetate in hexane

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

Procedure: To 6-bromo-4-fluoro-3-methoxyaniline (7.0 g, 32 mmol) was added conc. HCl (10 ml) followed by p-chloranil (7.80 g, 32 mmol), then nbutanol (10 ml) was added and the whole mix heated up to reflux, with stirring. A solution of crotonaldehyde (2.7 g 38.4 mmol) in nbutanol (5 ml), was added slowly over 0.5 h, and reflux continued for a further 0.5 h. The reaction mixture was allowed to cool, and the basified to pH14 using 50% NaOH solution. The reaction mixture was diluted with water (200 ml) and extracted with dichloromethane (3×100 ml). The combined organic extracts were dried over Na2SO4 and evaporated in vacuo to give a dark oil which was chromatographed on silica gel (˜200 g) eluting from 20% ethyl acetate in hexane to give the title compound as a brown oil (2.97 g, 34%). nbutanol (10 ml) was added the whole mix heated up to reflux reflux to cool extracted with dichloromethane (3×100 ml) The combined organic extracts were dried over Na2SO4 evaporated in vacuo to give a dark oil which was chromatographed on silica gel (˜200 g) eluting from 20% ethyl acetate in hexane

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

Procedure: A mixture of 4-fluoro-3-methoxyaniline (9.87 g, 70 mmol) and N-bromosuccinimide (12.46 g, 70 mmol) in dichloromethane (150 ml) was stirred at room temperature for 1 h (exothermic). The reaction mixture was evaporated in vacuo to give a dark slurry which was chromatographed on silica gel (˜350 g) using a gradient elution 20-50% ethyl acetate in hexane to give the title compound as a brown solid (12.70 g, 82%). The reaction mixture was evaporated in vacuo to give a dark slurry which was chromatographed on silica gel (˜350 g) a gradient elution 20-50% ethyl acetate in hexane

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

Procedure: To 6-bromo-4-fluoro-3-methoxyaniline (7.0 g, 32 mmol) was added conc. HCl (10 ml) followed by p-chloranil (7.80 g, 32 mmol), then nbutanol (10 ml) was added and the whole mix heated up to reflux, with stirring. A solution of crotonaldehyde (2.7 g 38.4 mmol) in nbutanol (5 ml), was added slowly over 0.5 h, and reflux continued for a further 0.5 h. The reaction mixture was allowed to cool, and the basified to pH14 using 50% NaOH solution. The reaction mixture was diluted with water (200 ml) and extracted with dichloromethane (3×100 ml). The combined organic extracts were dried over Na2SO4 and evaporated in vacuo to give a dark oil which was chromatographed on silica gel (˜200 g) eluting from 20% ethyl acetate in hexane to give the title compound as a brown oil (2.97 g, 34%). nbutanol (10 ml) was added the whole mix heated up to reflux reflux to cool extracted with dichloromethane (3×100 ml) The combined organic extracts were dried over Na2SO4 evaporated in vacuo to give a dark oil which was chromatographed on silica gel (˜200 g) eluting from 20% ethyl acetate in hexane

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

Procedure: A mixture of 4-fluoro-3-methoxyaniline (9.87 g, 70 mmol) and N-bromosuccinimide (12.46 g, 70 mmol) in dichloromethane (150 ml) was stirred at room temperature for 1 h (exothermic). The reaction mixture was evaporated in vacuo to give a dark slurry which was chromatographed on silica gel (˜350 g) using a gradient elution 20-50% ethyl acetate in hexane to give the title compound as a brown solid (12.70 g, 82%). The reaction mixture was evaporated in vacuo to give a dark slurry which was chromatographed on silica gel (˜350 g) a gradient elution 20-50% ethyl acetate in hexane