2-fluoroacetyl chloride

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:

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: Fluoroacetyl chloride (7.1 g, 73 mmoles) was added dropwise to a stirred solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (10.65 g, 74 mmoles) and pyridine (16.85 ml, 210 mmoles) in methylene chloride (75 ml) keeping the temperature below 10°. After stirring for 16 hours at room temperature the solution was diluted with methylene chloride (100 ml and then washed with 1N hydrochloric acid (200 ml) and water (100 ml). The organic extract was dried (Na2SO4) and the solvent removed in vacuo. The residue was dissolved in methanol (150 ml) and the solution heated at reflux for 2.5 hours. Removal of the solvent followed by distillation at 60°-80° (bath temp)/14 mm Hg gave methyl 4-fluoro-3-oxobutanoate (6.4 g). the temperature below 10° washed with 1N hydrochloric acid (200 ml) and water (100 ml) The organic extract was dried (Na2SO4) the solvent removed in vacuo The residue was dissolved in methanol (150 ml) the solution heated at reflux for 2.5 hours Removal of the solvent followed by distillation at 60°-80° (bath temp)/14 mm Hg

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

実験手順: To a stirred solution of N-(2-(3-(3-benzylazetidin-3-yl)phenoxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide (81 mg, 0.190 mmol) in dry dichloromethane (1.5 ml) containing diisopropylamine (0.066 ml, 0.380 mmol) under argon was added fluoroacetyl chloride (0.022 ml, 0.285 mmol) and stirred at room temperature for 1 h. Washed with 1N HCl, sodium bicarbonate and brine, dried over MgSO4, filtered, evaporated and the crude material was purified by flash silica gel chromatography on 4 g SiO2-cartridge using 5% MeOH in dichloromethane affording 68.7 mg of a white solid. Washed with 1N HCl, sodium bicarbonate and brine dried over MgSO4 filtered evaporated the crude material was purified by flash silica gel chromatography on 4 g SiO2-cartridge

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: Prepared as described in Example 1 using (1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3-methoxyphenyl)propan-2-amine (6a, 19 mg, 50 μmol) and fluoroacetyl chloride (14 mg, 150 μmol). Yield 16 mg (71%). Prepared

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

実験手順: Prepared as described in Example 1 using (1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3-methoxyphenyl)propan-2-amine (6a, 19 mg, 50 μmol) and fluoroacetyl chloride (14 mg, 150 μmol). Yield 16 mg (71%). Prepared

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

実験手順: Prepared as described in Example 1 using (1R,2S)-1-(4-ethylphenyl)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}propan-2-amine (7a, 20 mg, 50 μmol) and fluoroacetyl chloride (14 mg, 150 μmol). Yield 15 mg (65%). Prepared

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

実験手順: 1,3-Difluorobenzene (2.02 g; 17.7 mM) and anhydrous aluminium chloride (2.60 g; 19.47 mM) were stirred together under dry nitrogen at room temperature. A solution of fluoroacetyl chloride (1,71 g; 17.7 mM) in anhydrous methylene chloride (2 ml) was added over 30 minutes. The mixture was then warmed at about 50° for 3 hours. On cooling methylene chloride (40 ml) was added and the mixture was poured onto ice. The methylene chloride layer was separated, dried over magnesium sulphate and evaporated to give a white solid. This material was chromatographed on a column of silica eluting with a mixture of hexane/methylene chloride (65:35 by volume). The product-containing fractions were collected. The title compound crystallised on evaporation of these fractions and was dried in a vacuum desiccator to a colourless crystalline solid (1.12 g; 36% yield), melting point 57°-8°. The mixture was then warmed at about 50° for 3 hours was added the mixture was poured onto ice The methylene chloride layer was separated dried over magnesium sulphate evaporated to give a white solid This material was chromatographed on a column of silica eluting with a mixture of hexane/methylene chloride (65:35 by volume) The product-containing fractions were collected The title compound crystallised on evaporation of these fractions was dried in a vacuum desiccator to a colourless crystalline solid (1.12 g; 36% yield), melting point 57°-8°