4-bromo-3-fluorobenzenethiol

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 solution of 4-bromo-3-fluoro-benzenethiol (225 mg, 1.09 mmol) in tetrahydrofuran (3 ml) was cooled to 0° C. Sodium hydride (60% dispersion in mineral oil, 52 mg, 1.31 mmol) was added and the mixture was stirred for 5 minutes. Iodomethane (78 μl, 1.25 mmol) was then added and the mixture was allowed to return to room temperature with stirring over 20 minutes. Dichloromethane (10 ml) was added and the reaction was quenched with 1 M aqueous hydrochloric acid. The layers were separated and the organic layer was washed with water, dried (MgSO4), then concentrated in vacuo. The residue was purified by flash chromatography (Si-PPC, pentane:diethyl ether, gradient 100:0 to 90:10) to afford the title compound as a bright yellow oil (208 mg, 86%). 1H NMR (CDCl3, 400 MHz) 7.43 (1H, dd, J=8.4, 7.2), 7.00 (1H, dd, J=9.4, 2.3), 6.91 (1H, ddd, J=8.4, 2.1, 0.7), 2.48 (3H, s). to return to room temperature with stirring over 20 minutes the reaction was quenched with 1 M aqueous hydrochloric acid The layers were separated the organic layer was washed with water dried (MgSO4) concentrated in vacuo The residue was purified by flash chromatography (Si-PPC, pentane:diethyl ether, gradient 100:0 to 90:10)

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

実験手順: A solution of 4-bromo-3-fluoro-benzenethiol (225 mg, 1.09 mmol) in tetrahydrofuran (3 ml) was cooled to 0° C. Sodium hydride (60% dispersion in mineral oil, 52 mg, 1.31 mmol) was added and the mixture was stirred for 5 minutes. Iodomethane (78 μl, 1.25 mmol) was then added and the mixture was allowed to return to room temperature with stirring over 20 minutes. Dichloromethane (10 ml) was added and the reaction was quenched with 1 M aqueous hydrochloric acid. The layers were separated and the organic layer was washed with water, dried (MgSO4), then concentrated in vacuo. The residue was purified by flash chromatography (Si-PPC, pentane:diethyl ether, gradient 100:0 to 90:10) to afford the title compound as a bright yellow oil (208 mg, 86%). 1H NMR (CDCl3, 400 MHz) 7.43 (1H, dd, J=8.4, 7.2), 7.00 (1H, dd, J=9.4, 2.3), 6.91 (1H, ddd, J=8.4, 2.1, 0.7), 2.48 (3H, s). to return to room temperature with stirring over 20 minutes the reaction was quenched with 1 M aqueous hydrochloric acid The layers were separated the organic layer was washed with water dried (MgSO4) concentrated in vacuo The residue was purified by flash chromatography (Si-PPC, pentane:diethyl ether, gradient 100:0 to 90:10)

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

実験手順: 4-Bromo-3-fluoro-benzenesulfonyl chloride (324 μl, 2.19 mmol) was added dropwise to a solution of triphenylphosphine (1.73 g, 6.58 mmol) in a mixture of dimethylformamide (125 μl) and dichloromethane (5 ml). The solution was stirred at room temperature for 16 hours, then 1 M aqueous hydrochloric acid (5 ml) was added and the layers were separated. The organic layer was concentrated in vacuo and the resultant residue taken up in 1 M aqueous sodium hydroxide (10 ml). The resulting suspension was filtered through Celite® and the filtrate washed with ether (10 ml×3), then neutralised by addition of 1 M aqueous hydrochloric acid (10 ml). The solution was extracted with ether (10 ml×3) and the combined organic extracts were dried (Na2SO4) then concentrated in vacuo to afford the title compound as a colourless oil (225 mg, 50%). 1H NMR (CDCl3, 300 MHz) 7.47 (1H, dd, J=8.4, 7.5 Hz), 7.06 (1H, dd, J=8.9, 2.2 Hz), 6.93 (1H, ddd, J=8.4, 2.1, 0.7 Hz), 3.54 (1H, br s). the layers were separated The organic layer was concentrated in vacuo The resulting suspension was filtered through Celite® the filtrate washed with ether (10 ml×3) neutralised by addition of 1 M aqueous hydrochloric acid (10 ml) The solution was extracted with ether (10 ml×3) the combined organic extracts were dried (Na2SO4) then concentrated in vacuo

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

実験手順: 4-Bromo-3-fluoro-benzenesulfonyl chloride (324 μl, 2.19 mmol) was added dropwise to a solution of triphenylphosphine (1.73 g, 6.58 mmol) in a mixture of dimethylformamide (125 μl) and dichloromethane (5 ml). The solution was stirred at room temperature for 16 hours, then 1 M aqueous hydrochloric acid (5 ml) was added and the layers were separated. The organic layer was concentrated in vacuo and the resultant residue taken up in 1 M aqueous sodium hydroxide (10 ml). The resulting suspension was filtered through Celite® and the filtrate washed with ether (10 ml×3), then neutralised by addition of 1 M aqueous hydrochloric acid (10 ml). The solution was extracted with ether (10 ml×3) and the combined organic extracts were dried (Na2SO4) then concentrated in vacuo to afford the title compound as a colourless oil (225 mg, 50%). 1H NMR (CDCl3, 300 MHz) 7.47 (1H, dd, J=8.4, 7.5 Hz), 7.06 (1H, dd, J=8.9, 2.2 Hz), 6.93 (1H, ddd, J=8.4, 2.1, 0.7 Hz), 3.54 (1H, br s). the layers were separated The organic layer was concentrated in vacuo The resulting suspension was filtered through Celite® the filtrate washed with ether (10 ml×3) neutralised by addition of 1 M aqueous hydrochloric acid (10 ml) The solution was extracted with ether (10 ml×3) the combined organic extracts were dried (Na2SO4) then concentrated in vacuo

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of 4-bromo-3-fluorobenzenethiol (Preparation 26, 400 mg, 1.93 mmol), potassium tert-butoxide (238 mg, 2.12 mmol) and bromocyclopropane (701 mg, 5.80 mmol) in DMSO (10 mL) was heated at 90° C. for 16 hours. Additional potassium tert-butoxide (43 mg, 0.386 mmol) and bromocyclopropane (467 mg, 3.86 mmol) were added and heating continued at 90° C. for 30 hours. The mixture was cooled to room temperature and poured into 2-methoxy-2-methylpropane (30 mL). The mixture was washed with water (2×30 mL), dried over Na2SO4, concentrated in vacuo and purified by silica gel column chromatography eluting with heptanes to give the title compound as a colourless oil 27% yield, 130 mg. heating The mixture was cooled to room temperature The mixture was washed with water (2×30 mL) dried over Na2SO4 concentrated in vacuo purified by silica gel column chromatography eluting with heptanes

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of 4-bromo-3-fluorobenzenethiol (Preparation 26, 400 mg, 1.93 mmol), cesium carbonate (691 mg, 2.12 mmol) and bromocyclobutane (287 mg, 2.12 mmol) in DMSO (8 mL) was heated at 70° C. for 19 hours. The mixture was cooled to room temperature, poured into water (30 mL) and extracted with 2-methoxy-2-methylpropane (30 mL), washed with water (30 mL), dried over sodium sulfate and concentrated in vacuo. This gave the title compound as a colourless oil 95% yield, 480 mg. The mixture was cooled to room temperature extracted with 2-methoxy-2-methylpropane (30 mL) washed with water (30 mL) dried over sodium sulfate concentrated in vacuo

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

実験手順: A stirred ice-cooled solution of triphenylphosphine (23.0 g, 87.7 mmol), in CH2Cl2 (50 mL) and DMF (1.6 mL) was treated with a solution of 4-bromo-3-fluorobenzene-1-sulfonyl chloride (8.00 g, 29.2 mmol) in CH2Cl2 (50 mL) and stirred room temperature for 16 hours. The mixture was washed with 1N aqueous HCl (80 mL) and concentrated in vacuo. The resulting solid was diluted with 1N aqueous NaOH (160 mL), the solid filtered and the filtrate washed with 2-methoxy-2-methylpropane (3×150 mL) and acidified to pH 1 with 1M aqueous HCl. Extraction of the aqueous layer with 2-methoxy-2-methylpropane (3×100 mL), followed by drying over sodium sulphate and concentrating in vacuo gave the title compound as a yellow oil 66% yield, 3.97 g. The mixture was washed with 1N aqueous HCl (80 mL) concentrated in vacuo The resulting solid was diluted with 1N aqueous NaOH (160 mL) the solid filtered the filtrate washed with 2-methoxy-2-methylpropane (3×150 mL) Extraction of the aqueous layer with 2-methoxy-2-methylpropane (3×100 mL) by drying over sodium sulphate concentrating in vacuo