1-(4-chloro-2-fluorophenyl)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:

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

実験手順: Stir a mixture of heptanes (1.5 L), methanol (0.4 L), and 1-(4-chloro-2-fluorophenyl)ethanone (1 kg, 5.81 mol) with cooling to <5° C. Add sulfuryl chloride (0.608 L, 1.02 kg, 7.55 mol) as a heptanes (1.5 L) solution drop-wise to the mixture keeping the reaction temperature <15° C. during the addition. After 2 h quench the reaction at ambient temperature to a pH of 6 with sodium hydroxide (5N, 2.0 L). Extract the reaction mixture with methylene chloride (2 L) and concentrate the extract to form a white solid. Filter and dry the solid. with cooling to <5° C the reaction temperature <15° C. during the addition After 2 h quench the reaction at ambient temperature to a pH of 6 with sodium hydroxide (5N, 2.0 L) Extract the reaction mixture with methylene chloride (2 L) concentrate the extract to form a white solid Filter dry the solid

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

実験手順: Stir a mixture of heptanes (1.5 L), methanol (0.4 L), and 1-(4-chloro-2-fluorophenyl)ethanone (1 kg, 5.81 mol) with cooling to <5° C. Add sulfuryl chloride (0.608 L, 1.02 kg, 7.55 mol) as a heptanes (1.5 L) solution drop-wise to the mixture keeping the reaction temperature <15° C. during the addition. After 2 h quench the reaction at ambient temperature to a pH of 6 with sodium hydroxide (5N, 2.0 L). Extract the reaction mixture with methylene chloride (2 L) and concentrate the extract to form a white solid. Filter and dry the solid. with cooling to <5° C the reaction temperature <15° C. during the addition After 2 h quench the reaction at ambient temperature to a pH of 6 with sodium hydroxide (5N, 2.0 L) Extract the reaction mixture with methylene chloride (2 L) concentrate the extract to form a white solid Filter dry the solid

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 1 L round bottom flask combine 4′-chloro-2′-fluoroacetophenone (40 g, 231.8 mmol), heptane (120 mL), and methanol (16 mL). Cool to 0° C. and place under nitrogen. Dissolve sulfuryl chloride (21.5 mL, 1.15 equiv.) in heptane (120 mL) and charge to an addition funnel Add drop-wise to the reaction over 60 min. Stir for 2.5 h at 0° C.; a white precipitate forms during this time. Charge the addition funnel with 1 M sodium bicarbonate (400 mL) then add to the reaction drop-wise. After all gas evolution stops, filter the biphasic suspension to collect the title compound (38.18 g, 80%) as white needles. 1H NMR (DMSO-d6) δ 5.00 (d, 2H, J=2.5 Hz), 7.43 (m, 1H), 7.63 (m, 1H), 7.89 (t, 1H, J=8.4 Hz). In a 1 L round bottom flask combine Add drop-wise to the reaction over 60 min then add to the reaction drop-wise filter the biphasic suspension to collect the title compound (38.18 g, 80%) as white needles

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 starting from 4.22 g (24.14 mmol) of 4-bromofluorobenzene and 5.00 g (28.97 mmol) of 4-chloro-2-fluoroacetophenone in analogy to the synthesis of the compound from Example 176A. A difference was that the crude product was purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 9/1). 5.23 g (73% of theory) of the title compound were obtained. The title compound was prepared was purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 9/1)

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 starting from 4.22 g (24.14 mmol) of 4-bromofluorobenzene and 5.00 g (28.97 mmol) of 4-chloro-2-fluoroacetophenone in analogy to the synthesis of the compound from Example 176A. A difference was that the crude product was purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 9/1). 5.23 g (73% of theory) of the title compound were obtained. The title compound was prepared was purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 9/1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 114.6 ml (57.31 mmol) of a 0.5N solution of cyclopropylmagnesium bromide in tetrahydrofuran were taken up at 0° C. in 23 ml of diethyl ether, and 4.95 g (28.65 mmol) of 4′-chloro-2′-fluoroacetophenone dissolved in 5 ml of diethyl ether were slowly added dropwise. Stirring at 0° C. for 1 h was followed by warming to RT, and the reaction solution was mixed with acetonitrile, water and a little kieselguhr, and the mixture was filtered through kieselguhr. The phases of the filtrate were separated and the aqueous phase was extracted twice with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution and dried over sodium sulfate, and the solvents were removed in vacuo. The crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient) to result in 4.30 g (70% of theory) of the title compound. were slowly added dropwise by warming to RT a little kieselguhr, and the mixture was filtered through kieselguhr The phases of the filtrate were separated the aqueous phase was extracted twice with diethyl ether The combined organic phases were washed with saturated aqueous sodium chloride solution dried over sodium sulfate the solvents were removed in vacuo The crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 114.6 ml (57.31 mmol) of a 0.5N solution of cyclopropylmagnesium bromide in tetrahydrofuran were taken up at 0° C. in 23 ml of diethyl ether, and 4.95 g (28.65 mmol) of 4′-chloro-2′-fluoroacetophenone dissolved in 5 ml of diethyl ether were slowly added dropwise. Stirring at 0° C. for 1 h was followed by warming to RT, and the reaction solution was mixed with acetonitrile, water and a little kieselguhr, and the mixture was filtered through kieselguhr. The phases of the filtrate were separated and the aqueous phase was extracted twice with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution and dried over sodium sulfate, and the solvents were removed in vacuo. The crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient) to result in 4.30 g (70% of theory) of the title compound. were slowly added dropwise by warming to RT a little kieselguhr, and the mixture was filtered through kieselguhr The phases of the filtrate were separated the aqueous phase was extracted twice with diethyl ether The combined organic phases were washed with saturated aqueous sodium chloride solution dried over sodium sulfate the solvents were removed in vacuo The crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir: