1-(2-fluoro-4-hydroxyphenyl)ethanone

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

Procedure: 2-Fluoro-4-hydroxyacetophenone (15.14 g, 100 mmol) and zinc dust (19.61 g, 300 mmol) were suspended in 50 mL of H2O with stirring. Concentrated HCl (37%, 50 mL, 610 mmol) were added and the mixture was heated to reflux for six h. The reaction was cooled to rt, and diethyl ether was added. The mixture was saturated with NaCl, and filtered through celite washing with diethyl ether. The filtrate was poured into brine, and the layers were separated. The aqueous layer was extracted with diethyl ether. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 7.24 g (52%) of the title compound of step A. 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 7.00 (t, J=8.8 Hz, 1H), 6.52-6.40 (m, 2H), 2.44 (q, J=7.5 Hz, 2H), 1.06 (t, J=7.5 Hz, 3H). the mixture was heated to reflux for six h filtered through celite washing with diethyl ether The filtrate was poured into brine the layers were separated The aqueous layer was extracted with diethyl ether The combined organic layers were dried over MgSO4 filtered concentrated in vacuo The residue was purified by flash chromatography

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

Procedure: To a stirred solution of 1-(2-fluoro-4-hydroxyphenyl)-1-ethanone (2.56 g, 16.6 mmol) in dioxane (4 ml) was added a solution of bromine (2.70 g, 16.9 mmol) in dioxane (15 ml) dropwise, and the mixture was stirred for 3 hours. The volatile was evaporated in vacuo, and the residue was used for next reaction without purification. (2.4 g, 62% yield). The volatile was evaporated in vacuo the residue was used for next reaction without purification

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

Procedure: To a stirred suspension of aluminum chloride (42 g, 312 mmol) in 1,2-dichloroethane (100 ml) was added 3-fluorophenol (31 g, 276 mmol) dropwise at 0° C. After addition, acetyl chloride (24 g, 306 mmol) was added dropwise and then the mixture was heated at reflux temperature for 16 hours. The mixture was cooled down to room temperature, and poured into ice. The whole was extracted with diethylether. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was recystallized with hexane to give title compound (3.57 g, 8% yield). was added dropwise the mixture was heated at reflux temperature for 16 hours poured into ice The whole was extracted with diethylether The organic layer was washed with brine dried over MgSO4 concentrated in vacuo

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

Procedure: To a stirred solution of 1-(2-fluoro-4-hydroxyphenyl)-1-ethanone (2.56 g, 16.6 mmol) in dioxane (4 ml) was added a solution of bromine (2.70 g, 16.9 mmol) in dioxane (15 ml) dropwise, and the mixture was stirred at room temperature for 3 hours. The volatile was evaporated in vacuo, and the residue was used for next reaction without further purification. (2.4 g, 62% yield). The volatile was evaporated in vacuo the residue was used for next reaction without further purification

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

Procedure: To a stirred suspension of aluminum chloride (42 g, 312 mmol) in 1,2-dichloroethane (100 ml) was added 3-fluorophenol (31 g, 276 mmol) dropwise at 0° C. After addition, acetyl chloride (24 g, 306 mmol) was added dropwise and then the mixture was heated at reflux temperature for 16 hours. The mixture was cooled down to room temperature, and poured into ice. The whole was extracted with diethylether. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was recystallized with hexane to give title compound (3.57 g, 8% yield). was added dropwise the mixture was heated at reflux temperature for 16 hours poured into ice The whole was extracted with diethylether The organic layer was washed with brine dried over MgSO4 concentrated in vacuo

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

Procedure: To a solution of 5 g (32.44 mmol) of 1-(2-fluoro-4-hydroxyphenyl)ethanone dissolved in 140 ml of anhydrous dioxane are added dropwise 5.7 g (35.68 mmol, 1.83 ml) of dibromine at 0° C. under argon. The reaction mixture is brought to 70° C. for 3 h. The solvent is concentrated by vacuum evaporation and the solid is recrystallized in 40 ml of 1,2-dichloroethane to yield 5.67 g (75%) of 2-bromo-1-(2-fluoro-4-hydroxyphenyl)ethanone in the form of a violet solid. The solvent is concentrated by vacuum evaporation the solid is recrystallized in 40 ml of 1,2-dichloroethane

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

Procedure: 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 6 mmol of (2-fluoro-4-hydroxyphenyl)ethanone are treated as described in Example 56.

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

Procedure: 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 6 mmol of (2-fluoro-4-hydroxyphenyl)ethanone are treated as described in Example 56.

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

Procedure: Potassium carbonate (5.5 g, 40.0 mmol) and benzyl bromide (4.6 ml, 38.9 mmol) were added to a solution of 2-fluoro-4-hydroxyacetophenone (5.0 g, 32.4 mmol) in ethanol (50 ml), and the mixture was heated at reflux temperature for 16 h. The reaction mixture was evaporated to a residue to which 2 N HCl (100 ml) was added. This mixture was extracted with ethyl ether (3×60 ml) and the combined extracts were washed with brine (10 ml), dried (MgSO4), and evaporated to a residue, which was crystallized from ethyl acetate (7.4 g, 93%): MS(ES) m/z 245 (M+). the mixture was heated at reflux temperature for 16 h The reaction mixture was evaporated to a residue to which 2 N HCl (100 ml) was added This mixture was extracted with ethyl ether (3×60 ml) the combined extracts were washed with brine (10 ml) dried (MgSO4) evaporated to a residue, which was crystallized from ethyl acetate (7.4 g, 93%)

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

Procedure: To a stirred solution of 1-(2-fluoro-4-hydroxyphenyl)-1-ethanone (2.56 g, 16.6 mmol) in dioxane (4 ml) was added a solution of bromine (2.70 g, 16.9 mmol) in dioxane (15 ml) dropwise, and the mixture was stirred at room temperature for 3 hours. The volatile was evaporated in vacuo, and the residue was used for next reaction without further purification. (2.4 g, 62% yield). The volatile was evaporated in vacuo the residue was used for next reaction without further purification

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

Procedure: To a stirred suspension of aluminum chloride (42 g, 312 mmol) in 1,2-dichloroethane (100 ml) was added 3-fluorophenol (31 g, 276 mmol) dropwise at 0° C. After addition acetyl chloride (24 g, 306 mmol) was added dropwise and then the mixture was heated at reflux temperature for 16 hours. The mixture was cooled down to room temperature, and poured into ice. The whole was extracted with diethylether. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was recystallized with hexane to give title compound (3.57 g, 8% yield). was added dropwise the mixture was heated at reflux temperature for 16 hours poured into ice The whole was extracted with diethylether The organic layer was washed with brine dried over MgSO4 concentrated in vacuo

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

Procedure: To a stirred suspension of aluminum chloride (42 g, 312 mmol) in 1,2-dichloroethane (100 ml) was added 3-fluorophenol (31 g, 276 mmol) dropwise at 0° C. After addition acetyl chloride (24 g, 306 mmol) was added dropwise and then the mixture was heated at reflux temperature for 16 hours. The mixture was cooled down to room temperature, and poured into ice. The whole was extracted with diethylether. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was recystallized with hexane to give title compound (3.57 g, 8% yield). was added dropwise the mixture was heated at reflux temperature for 16 hours poured into ice The whole was extracted with diethylether The organic layer was washed with brine dried over MgSO4 concentrated in vacuo