1-(2-fluorophenyl)propan-1-one

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the 1-(2-fluoro-phenyl)-propan-1-one (99 mmol) in concentrated sulfuric acid (80 ml) cooled down to −30° C. was added slowly fuming nitric acid (8 ml) over 20 min and the solution was stirred at −30° C. for 15 min. The mixture was slowly poured into a stirred mixture of 200 ml of water and 400 g ice. The aqueous phase was extracted with ethyl acetate, the organic layer was extracted again with water and aqueous NaHCO3 1M. The organic layer was dried over Na2SO4, evaporated and the residue was purified by chromatography on silica using a mixture of heptane and ethylacetate as eluent to afford the pure nitro intermediate J. MS (ISP): m/z=198.1 [M+H]+. The aqueous phase was extracted with ethyl acetate the organic layer was extracted again with water and aqueous NaHCO3 1M The organic layer was dried over Na2SO4 evaporated the residue was purified by chromatography on silica using a mixture of heptane and ethylacetate as eluent

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

Procedure: To a solution of 2′-fluoropropiophenone (25.0 g) in acetic acid (250 mL) was slowly added bromine (8.4 mL). The mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. Water (200 mL) was added to the residue, and the mixture was extracted with diisopropyl ether. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (yield 36.8 g, 97%). concentrated under reduced pressure Water (200 mL) was added to the residue the mixture was extracted with diisopropyl ether The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a solution of 2′-fluoropropiophenone (25.0 g) in acetic acid (250 mL) was slowly added bromine (8.4 mL). The mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. Water (200 mL) was added to the residue, and the mixture was extracted with diisopropyl ether. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (yield 36.8 g, 97%). concentrated under reduced pressure Water (200 mL) was added to the residue the mixture was extracted with diisopropyl ether The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: This reaction is carried out in the same manner as the reaction in example 3. The difference is that, the reactants are p-methoxyphenyl chloride (142.3 mg, 1.0 mmol), 1-(2-fluorophenyl)-1-propanone (304.2 mg, 2.0 mmol), palladium acetate (6.8 mg, 0.030 mmol), 2-Methoxy-6-(N-methyl-N-phenyl-amino)phenyl(dicyclohexyl)phosphine (18.4 mg, 0.045 mmol), t-BuONa (192.7 mg, 2.0 mmol) in 3 mL dry toluene at 110° C. for 41.5 h. 1-(2′-Fluorophenyl)-2-(4′-methoxyphenyl)-1-propanon (134.7 mg) was obtained with a yield of 52% as liquid. 1H NMR (300 MHz, CDCl3) δ 7.76-7.68 (m, 1H, ArH), 7.44-7.34 (m, 1H, ArH), 7.20-7.08 (m, 3H, ArH), 7.07-6.98 (m, 1H, ArH), 6.83-6.77 (m, 2H, ArH), 4.57 (q, J=6.9 Hz, 1H, CH), 3.73 (s, 3H, OCH3), 1.52 (d, J=6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 199.8 (d, J=3.8 Hz), 160.7 (d, J=251.9 Hz), 158.5, 133.8 (d, J=8.8 Hz), 132.3, 130.9 (d, J=2.8 Hz), 129.1, 126.0 (d, J=12.8 Hz), 124.2 (d, J=3.9 Hz), 116.4 (d, J=23.7 Hz), 114.0, 55.0, 50.9 (d, J=5.9 Hz), 18.8; 19F NMR (282 MHz, CDCl3) 6-100.1; IR (neat) v (cm−1) 3069, 3034, 2974, 2933, 2871, 2836, 1682, 1609, 1582, 1513, 1480, 1451, 1422, 1373, 1324, 1303, 1274, 1254, 1211, 1179, 1153, 1105, 1034, 1005; MS (70 eV, EI) m/z (%): 259 (M++1, 0.99), 258 (M+, 5.49), 135 (100); HRMS calcd for C16H15O2F (M+): 258.1056. Found: 258.1057. This reaction is carried out in the same manner as the reaction in example 3 at 110° C. for 41.5 h

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

Procedure: To a solution of 2′-fluoropropiophenone (25.0 g) in acetic acid (250 mL) was slowly added bromine (8.4 mL). The mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. To the residue was added water (200 mL), and the mixture was extracted with diisopropyl ether. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The filtrate was concentrated under reduced pressure to give the title compound as a yellow oil (yield 36.8 g, 97%). concentrated under reduced pressure To the residue was added water (200 mL) the mixture was extracted with diisopropyl ether The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous magnesium sulfate filtrated The filtrate was concentrated under reduced pressure

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the 1-(2-fluoro-phenyl)-propan-1-one (99 mmol) in concentrated sulfuric acid (80 ml) cooled down to −30° C. was added slowly fuming nitric acid (8 ml) over 20 min and the solution was stirred at −30° C. for 15 min. The mixture was slowly poured into a stirred mixture of 200 ml of water and 400 g ice. The aqueous phase was extracted with ethyl acetate, the organic layer was extracted again with water and aqueous NaHCO3 1M. The organic layer was dried over Na2SO4, evaporated and the residue was purified by chromatography on silica using a mixture of heptane and ethylacetate as eluent to afford the pure nitro intermediate J. MS (ISP): m/z=198.1 [M+H]+. The aqueous phase was extracted with ethyl acetate the organic layer was extracted again with water and aqueous NaHCO3 1M The organic layer was dried over Na2SO4 evaporated the residue was purified by chromatography on silica using a mixture of heptane and ethylacetate as eluent

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the 1-(2-fluoro-phenyl)-propan-1-one (99 mmol) in concentrated sulfuric acid (80 ml) cooled down to −30° C. was added slowly fuming nitric acid (8 ml) over 20 min and the solution was stirred at −30° C. for 15 min. The mixture was slowly poured into a stirred mixture of 200 ml of water and 400 g ice. The aqueous phase was extracted with ethyl acetate, the organic layer was extracted again with water and aqueous NaHCO3 1M. The organic layer was dried over Na2SO4, evaporated and the residue was purified by chromatography on silica using a mixture of heptane and ethylacetate as eluent to afford the pure nitro intermediate J. MS (ISP): m/z=198.1 [M+H]+. The aqueous phase was extracted with ethyl acetate the organic layer was extracted again with water and aqueous NaHCO3 1M The organic layer was dried over Na2SO4 evaporated the residue was purified by chromatography on silica using a mixture of heptane and ethylacetate as eluent

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

Procedure: To a solution of 2′-fluoropropiophenone (25.0 g) in acetic acid (250 mL) was slowly added bromine (8.4 mL). The mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. Water (200 mL) was added to the residue, and the mixture was extracted with diisopropyl ether. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (yield 36.8 g, 97%). concentrated under reduced pressure Water (200 mL) was added to the residue the mixture was extracted with diisopropyl ether The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a solution of 2′-fluoropropiophenone (25.0 g) in acetic acid (250 mL) was slowly added bromine (8.4 mL). The mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. Water (200 mL) was added to the residue, and the mixture was extracted with diisopropyl ether. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (yield 36.8 g, 97%). concentrated under reduced pressure Water (200 mL) was added to the residue the mixture was extracted with diisopropyl ether The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a solution of 2′-fluoropropiophenone (25.0 g) in acetic acid (250 mL) was slowly added bromine (8.4 mL). The mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. Water (200 mL) was added to the residue, and the mixture was extracted with diisopropyl ether. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (yield 36.8 g, 97%). concentrated under reduced pressure Water (200 mL) was added to the residue the mixture was extracted with diisopropyl ether The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a solution of 2′-fluoropropiophenone (25.0 g) in acetic acid (250 mL) was slowly added bromine (8.4 mL). The mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. Water (200 mL) was added to the residue, and the mixture was extracted with diisopropyl ether. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (yield 36.8 g, 97%). concentrated under reduced pressure Water (200 mL) was added to the residue the mixture was extracted with diisopropyl ether The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a solution of 2′-fluoropropiophenone (25.0 g) in acetic acid (250 mL) was slowly added bromine (8.4 mL). The mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. Water (200 mL) was added to the residue, and the mixture was extracted with diisopropyl ether. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (yield 36.8 g, 97%). concentrated under reduced pressure Water (200 mL) was added to the residue the mixture was extracted with diisopropyl ether The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure