1-(4-chloro-3-fluorophenyl)propan-2-one

Conditions: temp:76.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methylmagnesium bromide (100 mL, 100.0 mmol, 1.0 M in THF) was added a solution of 1-(4-chloro-3-fluorophenyl)propan-2-one (9.00 g, 48.20 mmol) in THF (20 mL) dropwise at 0° C. under N2 and the reaction mixture was heated at 76° C. for 12 h. It was then cooled to rt and quenched with saturated NH4Cl aqueous solution (50 mL) and the mixture was poured into water (200 mL). The resulting mixture was extracted with EtOAc (100 mL×4) and the combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 (50 g) and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=8:1) to give the title compound as yellow liquid (8.61 g, 88.2%). It was then cooled to rt quenched with saturated NH4Cl aqueous solution (50 mL) the mixture was poured into water (200 mL) The resulting mixture was extracted with EtOAc (100 mL×4) the combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 (50 g) concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=8:1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-1-chloro-2-fluorobenzene (20.90 g, 100.0 mmol) and acetylacetone (30 mL, 300.0 mmol) in DMSO (100 mL) were added tripotassium phosphate (63.70 g, 300.0 mmol) and CuI (3.00 g, 15.80 mmol) under N2 and the mixture was stirred at 110° C. for 23 h. The mixture was cooled to rt and hydrochloric acid (300 mL, 2 M) was added. The resulting mixture was extracted with EtOAc (100 mL×3) and the combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 (50 g), and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1) to give the title compound as yellow liquid (9.02 g, 48.2%). The mixture was cooled to rt The resulting mixture was extracted with EtOAc (100 mL×3) the combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 (50 g) filtered The filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1)

Conditions: temp:76.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methylmagnesium bromide (100 mL, 100.0 mmol, 1.0 M in THF) was added a solution of 1-(4-chloro-3-fluorophenyl)propan-2-one (9.00 g, 48.20 mmol) in THF (20 mL) dropwise at 0° C. under N2 and the reaction mixture was heated at 76° C. for 12 h. It was then cooled to rt and quenched with saturated NH4Cl aqueous solution (50 mL) and the mixture was poured into water (200 mL). The resulting mixture was extracted with EtOAc (100 mL×4) and the combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 (50 g) and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=8:1) to give the title compound as yellow liquid (8.61 g, 88.2%). It was then cooled to rt quenched with saturated NH4Cl aqueous solution (50 mL) the mixture was poured into water (200 mL) The resulting mixture was extracted with EtOAc (100 mL×4) the combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 (50 g) concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=8:1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-1-chloro-2-fluorobenzene (20.90 g, 100.0 mmol) and acetylacetone (30 mL, 300.0 mmol) in DMSO (100 mL) were added tripotassium phosphate (63.70 g, 300.0 mmol) and CuI (3.00 g, 15.80 mmol) under N2 and the mixture was stirred at 110° C. for 23 h. The mixture was cooled to rt and hydrochloric acid (300 mL, 2 M) was added. The resulting mixture was extracted with EtOAc (100 mL×3) and the combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 (50 g), and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1) to give the title compound as yellow liquid (9.02 g, 48.2%). The mixture was cooled to rt The resulting mixture was extracted with EtOAc (100 mL×3) the combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 (50 g) filtered The filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1)

Conditions: temp:76.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methylmagnesium bromide (100 mL, 100.0 mmol, 1.0 M in THF) was added a solution of 1-(4-chloro-3-fluorophenyl)propan-2-one (9.00 g, 48.20 mmol) in THF (20 mL) dropwise at 0° C. under N2 and the reaction mixture was heated at 76° C. for 12 h. It was then cooled to rt and quenched with saturated NH4Cl aqueous solution (50 mL) and the mixture was poured into water (200 mL). The resulting mixture was extracted with EtOAc (100 mL×4) and the combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 (50 g) and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=8:1) to give the title compound as yellow liquid (8.61 g, 88.2%). It was then cooled to rt quenched with saturated NH4Cl aqueous solution (50 mL) the mixture was poured into water (200 mL) The resulting mixture was extracted with EtOAc (100 mL×4) the combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 (50 g) concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=8:1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-1-chloro-2-fluorobenzene (20.90 g, 100.0 mmol) and acetylacetone (30 mL, 300.0 mmol) in DMSO (100 mL) were added tripotassium phosphate (63.70 g, 300.0 mmol) and CuI (3.00 g, 15.80 mmol) under N2 and the mixture was stirred at 110° C. for 23 h. The mixture was cooled to rt and hydrochloric acid (300 mL, 2 M) was added. The resulting mixture was extracted with EtOAc (100 mL×3) and the combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 (50 g), and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1) to give the title compound as yellow liquid (9.02 g, 48.2%). The mixture was cooled to rt The resulting mixture was extracted with EtOAc (100 mL×3) the combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 (50 g) filtered The filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1)