methyl 3-(4-fluorophenyl)propanoate

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: Crude methyl 2-bromo-3-(4-fluorophenyl)propionate in acetic acid (330 ml) was stirred and treated with zinc dust (32.75 g) in portions over 30 minutes. The mixture was stirred for an additional 30 minutes and filtered, and the filter cake was washed with acetic acid. After the filtrate was evaporated the residue was partitioned between methylene chloride and water to give crude methyl 3-(4-fluorophenyl)propionate, which was refluxed with aqueous sodium hydroxide (400 ml, 10%) for 2 hrs, cooled, treated with decolorizing carbon, and filtered. The filtrate was acidified with 5 N HCl and filtered. The filter cake was washed extensively with water to give 3-(4-fluorophenyl)propionic acid (20.0 g) as colourless crystals, mp 90° C. filtered the filter cake was washed with acetic acid After the filtrate was evaporated the residue was partitioned between methylene chloride and water

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

実験手順: Sodium metaperiodate (0.971 g, 4.54 mmol) was slowly added to a solution of iodine (3.43 g, 13.5 mmol) in sulfuric acid (86 ml). This was stirred at room temperature for 30 minutes. This dark brown iodinating solution was then slowly added to a solution of methyl 3-(4-fluorophenyl)propanoate (5.20 g, 28.5 mmol) in sulfuric acid (28.5 ml) (pre-cooled to 0° C.) taking care not to let the temperature rise above 30° C. This was stirred for 50 min. further, and then the reaction was quenched by pouring onto 100 mL of stirring ice water. This was extracted with ethyl acetate (2×100 mL) and the combined organic layers were washed with water (100 mL) and brine (100 mL). The organic layer was dried over sodium sulfate and purified via column chromatography on a Biotage 40M column eluting with hexanes (1 CV) followed by a gradient of 0-50% ethyl acetate in hexanes to provide the desired product as a clear colorless liquid. 1H NMR (CDCl3, 500 MHz) δ 7.58 (dd, J=5.8 Hz, 1.9 Hz, 1H), 7.13 (m, 1H), 6.96 (t, J=8.2 Hz, 1H), 3.67 (s, 3H), 2.88 (t, J=7.7 Hz, 2H), 2.61 (t, J=7.7 Hz, 2H). rise above 30° C This was stirred for 50 min. further the reaction was quenched by pouring onto 100 mL of stirring ice water This was extracted with ethyl acetate (2×100 mL) the combined organic layers were washed with water (100 mL) and brine (100 mL) The organic layer was dried over sodium sulfate purified via column chromatography on a Biotage 40M column eluting with hexanes (1 CV)

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

実験手順: To a solution of 3-(4-fluorophenyl)propionic acid (4.75 g, 28.2 mmol) in toluene (130 mL) and methanol (20 mL) was added trimethylsilyldiazomethane (2M solution in hexane, 16.24 mL, 32.5 mmol). The mixture was allowed to stir for 1 hour and gas evolution was observed initially. After 1 hour, the mixture became homogeneous and was quenched via addition of 3.5 mL of acetic acid. The mixture was concentrated in vacuo, and purified via column chromatography on a Biotage 65i column eluting with 0% ethyl acetate in hexanes (1 CV) followed by a gradient to 50% ethyl acetate in hexanes (over 7 CV) to furnish the desired product. 1H NMR (CDCl3, 500 MHz) δ 7.16 (dd, J=8.0 Hz, 5.6 Hz, 2H), 6.97 (t, J=8.5 Hz, 2H), 3.66 (s, 3H), 2.92 (t, J=7.5 Hz, 2H), 2.61 (t, J=7.7 Hz, 2H). After 1 hour was quenched via addition of 3.5 mL of acetic acid The mixture was concentrated in vacuo purified via column chromatography on a Biotage 65i column eluting with 0% ethyl acetate in hexanes (1 CV)

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

実験手順: Crude methyl 2-bromo-3-(4-fluorophenyl)propionate in acetic acid (330 ml) was stirred and treated with zinc dust (32.75 g) in portions over 30 minutes. The mixture was stirred for an additional 30 minutes and filtered, and the filter cake was washed with acetic acid. After the filtrate was evaporated the residue was partitioned between methylene chloride and water to give crude methyl 3-(4-fluorophenyl)propionate, which was refluxed with aqueous sodium hydroxide (400 ml, 10%) for 2 hrs, cooled, treated with decolorizing carbon, and filtered. The filtrate was acidified with 5 N HCl and filtered. The filter cake was washed extensively with water to give 3-(4-fluorophenyl)propionic acid (20.0 g) as colourless crystals, mp 90° C. filtered the filter cake was washed with acetic acid After the filtrate was evaporated the residue was partitioned between methylene chloride and water