sulfuric acid 18 h; Heating / reflux;

1: 5,6-Dichloronicotinic acid With thionyl chloride; N,N-dimethyl-formamide T=105°C; 1 h; 2: methanol T=0 - 20°C; 0.5 h;

in methanol; hexanes; toluene T=0°C; 12 - 18 h;

in pyridine

thionyl chloride in methanol; ethyl acetate

potassium fluoride; chloro-difluoro-acetic acid methyl ester; copper(II) bis(trifluoromethanesulfonate) in N,N-dimethyl acetamide T=120°C;

potassium fluoride; (CuOTf)2.C6H6; chloro-difluoro-acetic acid methyl ester in N,N-dimethyl acetamide T=120°C; Reagent/catalyst;

1: sulfuric acid / 22 h / |Reflux; |Large scale 2: N-iodo-succinimide / methanol / 2 h / |Reflux; |Large scale 3: trichlorophosphate; N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 7 h / 100 °C / |Large scale 4: chloro-difluoro-acetic acid methyl ester; potassium fluoride; copper(II) bis(trifluoromethanesulfonate) / N,N-dimethyl acetamide / 120 °C View Scheme

1: N-iodo-succinimide / methanol / 2 h / |Reflux; |Large scale 2: trichlorophosphate; N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 7 h / 100 °C / |Large scale 3: chloro-difluoro-acetic acid methyl ester; potassium fluoride; copper(II) bis(trifluoromethanesulfonate) / N,N-dimethyl acetamide / 120 °C View Scheme

1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 7 h / 100 °C / |Large scale 2: chloro-difluoro-acetic acid methyl ester; potassium fluoride; copper(II) bis(trifluoromethanesulfonate) / N,N-dimethyl acetamide / 120 °C View Scheme