2-(2-chloro-5-fluorophenyl)acetaldehyde

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

Procedure: To a slurry of potassium tert-butoxide (94 mg, 0.8 mmol) in 1,4-dioxane (1 mL) cooled at 0° C. was added 2-(2-chloro-5-fluorophenyl)acetaldehyde (98 mg, 0.4 mmol) as a solution in 1,4-dioxane (0.6 mL). The reaction mixture was stirred for 10 minutes at this temperature, and then tert-butyl 2-bromo-5-formylpyridin-4-ylcarbamate (60 mg, 0.2 mmol) was added as a solution in dioxane (0.6 mL). The reaction mixture was allowed to warm to room temperature, and after 30 minutes a 5.0M solution of hydrogen chloride in water (0.5 mL) was added and the mixture was heated at 100° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as an off-white solid (20 mg, 30%), which was used in the next step without further purification. the mixture was heated at 100° C. for 1 hour The cooled reaction mixture washed with water (50 mL) The organic layer was separated dried over sodium sulfate filtered evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane)

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

Procedure: To a slurry of potassium tert-butoxide (94 mg, 0.8 mmol) in 1,4-dioxane (1 mL) cooled at 0° C. was added 2-(2-chloro-5-fluorophenyl)acetaldehyde (98 mg, 0.4 mmol) as a solution in 1,4-dioxane (0.6 mL). The reaction mixture was stirred for 10 minutes at this temperature, and then tert-butyl 2-bromo-5-formylpyridin-4-ylcarbamate (60 mg, 0.2 mmol) was added as a solution in dioxane (0.6 mL). The reaction mixture was allowed to warm to room temperature, and after 30 minutes a 5.0M solution of hydrogen chloride in water (0.5 mL) was added and the mixture was heated at 100° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as an off-white solid (20 mg, 30%), which was used in the next step without further purification. the mixture was heated at 100° C. for 1 hour The cooled reaction mixture washed with water (50 mL) The organic layer was separated dried over sodium sulfate filtered evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane)

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

Procedure: To a slurry of potassium tert-butoxide (94 mg, 0.8 mmol) in 1,4-dioxane (1 mL) cooled at 0° C. was added 2-(2-chloro-5-fluorophenyl)acetaldehyde (98 mg, 0.4 mmol) as a solution in 1,4-dioxane (0.6 mL). The reaction mixture was stirred for 10 minutes at this temperature, and then tert-butyl 2-bromo-5-formylpyridin-4-ylcarbamate (60 mg, 0.2 mmol) was added as a solution in dioxane (0.6 mL). The reaction mixture was allowed to warm to room temperature, and after 30 minutes a 5.0M solution of hydrogen chloride in water (0.5 mL) was added and the mixture was heated at 100° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as an off-white solid (20 mg, 30%), which was used in the next step without further purification. the mixture was heated at 100° C. for 1 hour The cooled reaction mixture washed with water (50 mL) The organic layer was separated dried over sodium sulfate filtered evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane)