1-(2,3-difluorophenyl)ethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2',3'-difluoroacetophenone (30 g), methylamine (33% w/w solution in industrial methylated spirit, 46.5 ml), industrial methylated spirit (20 ml) and copper powder (1 g) was stirred in a sealed pressure vessel overnight at 100°. The reaction mixture was allowed to cool to ambient temperature and the mixture washed out of the vessel with industrial methylated spirit (2×30 ml). A solution of sodium sulphide nonahydrate (3.7 g) in water (39 ml) was added and the mixture heated at 50° for 15 minutes. The mixture was filtered through diatomaceous earth (sold under the trade name CELITE) and the filter bed washed with industrial methylated spirit (50 ml). The combined filtrate and washing were evaporated to give an oil which was stirred with hydrochloric acid (5M, 120 ml) for 90 minutes. The mixture was neutralised with aqueous sodium hydroxide (5M, 120 ml) and then extracted with dichloromethane (2×150 ml, then 100 ml). The combined extracts were washed with aqueous sodium chloride (6M, 50 ml), dried over magnesium sulphate and evaporated to dryness. The residue was purified by flash chromatography on a silica gel column eluted with dichloromethane:methanol (19:1) to give the novel compound 3'-fluoro-2'-(methylamino)acetophenone, m.p. 26°-28°. the mixture washed out of the vessel with industrial methylated spirit (2×30 ml) A solution of sodium sulphide nonahydrate (3.7 g) in water (39 ml) was added the mixture heated at 50° for 15 minutes The mixture was filtered through diatomaceous earth ( washed with industrial methylated spirit (50 ml) The combined filtrate and washing were evaporated to give an oil which extracted with dichloromethane (2×150 ml The combined extracts were washed with aqueous sodium chloride (6M, 50 ml) dried over magnesium sulphate evaporated to dryness The residue was purified by flash chromatography on a silica gel column eluted with dichloromethane:methanol (19:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,3-difluoroacetophenone (25.0 g, 160 mmol) in THF (500 mL) was added (R)-(+)-2-methyl-2-propanesulfinamide (38.8 g, 320 mmol) followed by tetraisopropoxytitanium (142 mL, 480 mmol). The reaction was heated to reflux for 3 days. The mixture was allowed to cool to room temperature and then treated with brine (550 ml). The resulted suspension was stirred for 15 min and filtered through celite. The filter cake was washed with EtOAc. The filtrate was extracted with EtOAc (2×). The organic extracts were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and purified by silica gel column (10-35% EtOAc/hexane) to afford (R,Z)-N-(1-(2,3-difluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (35.6 g, 137 mmol, 86% yield) as yellow oil. MS m/z=260.1 [M+H]+ calculated for C12H15F2NOS: 259.3 The reaction was heated to reflux for 3 days filtered through celite The filter cake was washed with EtOAc The filtrate was extracted with EtOAc (2×) The organic extracts were washed with brine dried over Na2SO4 filtered The filtrate was concentrated purified by silica gel column (10-35% EtOAc/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2′,3′-Difluoroacetophenone (0.337 g, 2.16 mmol) in methanol (15 mL) was treated with sodium borohydride (0.090 g, 2.37 mmol), and the reaction was stirred at room temperature for 30 minutes. The mixture was partitioned between dichloromethane and water, and the organic layer was separated, dried over MgSO4, filtered, and concentrated to give 1-(2,3-difluoro-phenyl)-ethanol. The mixture was partitioned between dichloromethane and water the organic layer was separated dried over MgSO4 filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 2′,3′-difluoroacetophenone using the procedures outlined for 6-(4-fluorophenyl)nicotinic acid (D1-D3).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 2′,3′-difluoroacetophenone using the procedures outlined for 6-(4-fluorophenyl)nicotinic acid (D1-D3).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2',3'-difluoroacetophenone (30 g), methylamine (33% w/w solution in industrial methylated spirit, 46.5 ml), industrial methylated spirit (20 ml) and copper powder (1 g) was stirred in a sealed pressure vessel overnight at 100°. The reaction mixture was allowed to cool to ambient temperature and the mixture washed out of the vessel with industrial methylated spirit (2×30 ml). A solution of sodium sulphide nonahydrate (3.7 g) in water (39 ml) was added and the mixture heated at 50° for 15 minutes. The mixture was filtered through diatomaceous earth (sold under the trade name CELITE) and the filter bed washed with industrial methylated spirit (50 ml). The combined filtrate and washing were evaporated to give an oil which was stirred with hydrochloric acid (5M, 120 ml) for 90 minutes. The mixture was neutralised with aqueous sodium hydroxide (5M, 120 ml) and then extracted with dichloromethane (2×150 ml, then 100 ml). The combined extracts were washed with aqueous sodium chloride (6M, 50 ml), dried over magnesium sulphate and evaporated to dryness. The residue was purified by flash chromatography on a silica gel column eluted with dichloromethane:methanol (19:1) to give the novel compound 3'-fluoro-2'-(methylamino)acetophenone, m.p. 26°-28°. the mixture washed out of the vessel with industrial methylated spirit (2×30 ml) A solution of sodium sulphide nonahydrate (3.7 g) in water (39 ml) was added the mixture heated at 50° for 15 minutes The mixture was filtered through diatomaceous earth ( washed with industrial methylated spirit (50 ml) The combined filtrate and washing were evaporated to give an oil which extracted with dichloromethane (2×150 ml The combined extracts were washed with aqueous sodium chloride (6M, 50 ml) dried over magnesium sulphate evaporated to dryness The residue was purified by flash chromatography on a silica gel column eluted with dichloromethane:methanol (19:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2',3'-difluoroacetophenone (30 g), methylamine (33% w/w solution in industrial methylated spirit, 46.5 ml), industrial methylated spirit (20 ml) and copper powder (1 g) was stirred in a sealed pressure vessel overnight at 100°. The reaction mixture was allowed to cool to ambient temperature and the mixture washed out of the vessel with industrial methylated spirit (2×30 ml). A solution of sodium sulphide nonahydrate (3.7 g) in water (39 ml) was added and the mixture heated at 50° for 15 minutes. The mixture was filtered through diatomaceous earth (sold under the trade name CELITE) and the filter bed washed with industrial methylated spirit (50 ml). The combined filtrate and washing were evaporated to give an oil which was stirred with hydrochloric acid (5M, 120 ml) for 90 minutes. The mixture was neutralised with aqueous sodium hydroxide (5M, 120 ml) and then extracted with dichloromethane (2×150 ml, then 100 ml). The combined extracts were washed with aqueous sodium chloride (6M, 50 ml), dried over magnesium sulphate and evaporated to dryness. The residue was purified by flash chromatography on a silica gel column eluted with dichloromethane:methanol (19:1) to give the novel compound 3'-fluoro-2'-(methylamino)acetophenone, m.p. 26°-28°. the mixture washed out of the vessel with industrial methylated spirit (2×30 ml) A solution of sodium sulphide nonahydrate (3.7 g) in water (39 ml) was added the mixture heated at 50° for 15 minutes The mixture was filtered through diatomaceous earth ( washed with industrial methylated spirit (50 ml) The combined filtrate and washing were evaporated to give an oil which extracted with dichloromethane (2×150 ml The combined extracts were washed with aqueous sodium chloride (6M, 50 ml) dried over magnesium sulphate evaporated to dryness The residue was purified by flash chromatography on a silica gel column eluted with dichloromethane:methanol (19:1)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Bromine (4.96 g, 31.1 mmol) was slowly added dropwise to a solution of 1-(2,3-difluorophenyl)ethanone (4.85 g, 31.1 mmol) in diethyl ether (100 ml), and the mixture was stirred at room temperature for 5 hours. The reaction mixture was distilled off under reduced pressure to give 7.29 g (99.9%) of the desired product as an oil. The reaction mixture was distilled off under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Bromine (4.96 g, 31.1 mmol) was slowly added dropwise to a solution of 1-(2,3-difluorophenyl)ethanone (4.85 g, 31.1 mmol) in diethyl ether (100 ml), and the mixture was stirred at room temperature for 5 hours. The reaction mixture was distilled off under reduced pressure to give 7.29 g (99.9%) of the desired product as an oil. The reaction mixture was distilled off under reduced pressure