methyl 5-bromo-2,4-difluorobenzoate

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

Procedure: A mixture of 4-chlorophenol (94.7 mg, 0.74 mmol), methyl 5-bromo-2,4-difluorobenzoate (Preparation 18, 168 mg, 0.67 mmol), and potassium carbonate (277 mg, 2.01 mmol) in dimethyl sulfoxide (3 mL) was stirred for 16 hours at room temperature under a nitrogen atmosphere. The reaction was diluted with water (30 mL) and extracted with EtOAc (3×20 mL). The combined organic extracts were successively washed with aqueous sodium hydroxide solution (1.0 M, 20 mL), brine (2×30 mL), dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound as a colourless oil (199 mg, 83%). extracted with EtOAc (3×20 mL) The combined organic extracts were successively washed with aqueous sodium hydroxide solution (1.0 M, 20 mL), brine (2×30 mL) dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated hydrochloric acid (10.4 mL, 127 mmol) was slowly added to a mixture of 5-bromo-2,4-difluorobenzoic acid (0.999 g, 4.21 mmol) in methanol (26 mL). The mixture was heated at 95° C. for 18 hours. The reaction was cooled and then concentrated in vacuo. The residue was diluted with water (50 mL) and extracted with EtOAc (3×50 mL). The combined organic extract was washed with brine (2×50 mL), dried over sodium sulfate, filtered and concentrated in vacuo to afford a brown oil (0.847 g). The crude product was purified by silica gel chromatography (Biotage®, 100 g SNAP cartridge, 5 to 50% EtOAc in Heptane) to afford the title compound as clear crystalline solid (0.544 g). The reaction was cooled concentrated in vacuo The residue was diluted with water (50 mL) extracted with EtOAc (3×50 mL) The combined organic extract was washed with brine (2×50 mL) dried over sodium sulfate filtered concentrated in vacuo

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

Procedure: Prepared according to Preparation 3 with 4-chloro-2-methoxyphenol (0.13 mL, 1.07 mmol) and methyl 5-bromo-2,4-difluorobenzoate (Preparation 18, 255 mg, 1.02 mmol) at room temperature for 18 hours. The crude product was purified by silica gel chromatography eluting with 5% EtOAc in Heptane to afford the title compound as a white solid (0.165 g). Prepared The crude product was purified by silica gel chromatography eluting with 5% EtOAc in Heptane