2-(2,4-二氟苯基)环戊烷-1-one

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=266.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.19-8.64 (1H, m), 7.10 (1H, td, J=8.5, 6.3 Hz), 6.78-6.92 (2H, m), 4.36-4.49 (1H, m), 2.79-2.92 (1H, m), 2.59-2.78 (2H, m), 2.08 (1H, ddd, J=9.3, 6.9, 6.7 Hz). washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=265.1. washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 90% formic acid (26.4 mL, 689 mmol) and 30% hydrogen peroxide (6.0 mL, 39.2 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-cyclopentenyl-2,4-difluorobenzene (7.064 g, 39.2 mmol) under stirring. The two-phase system was initially stirred at room temperature. After a certain period of time, a spontaneous exothermic reaction took place, and the temperature rose to about 50° C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the content of the separatory funnel was vigorously shaken. The organic layer was separated and the aqueous layer was extracted with ether. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 2-(2,4-difluorophenyl)cyclopentanone (3.503 g, 17.85 mmol, 45.5% yield) as colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.08 (1H, td, J=8.4, 6.4 Hz), 6.76-6.86 (2H, m), 3.42 (1H, dd, J=12.2, 8.9 Hz), 2.42-2.53 (2H, m), 2.28-2.39 (1H, m), 2.13-2.23 (1H, m), 1.86-2.10 (2H, m). The two-phase system was initially stirred at room temperature After a certain period of time a spontaneous exothermic reaction rose to about 50° C The reaction mixture was stirred at room temperature for 2 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the content of the separatory funnel was vigorously shaken The organic layer was separated the aqueous layer was extracted with ether The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as a brown solid. LC-MS (M+H)+=266.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.19-8.64 (1H, m), 7.10 (1H, td, J=8.5, 6.3 Hz), 6.78-6.92 (2H, m), 4.36-4.49 (1H, m), 2.79-2.92 (1H, m), 2.59-2.78 (2H, m), 2.08 (1H, ddd, J=9.3, 6.9, 6.7 Hz). washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuo the residue was purified by column chromatography on silica gel

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as a brown solid. LC-MS (M+H)+=266.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.19-8.64 (1H, m), 7.10 (1H, td, J=8.5, 6.3 Hz), 6.78-6.92 (2H, m), 4.36-4.49 (1H, m), 2.79-2.92 (1H, m), 2.59-2.78 (2H, m), 2.08 (1H, ddd, J=9.3, 6.9, 6.7 Hz). washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuo the residue was purified by column chromatography on silica gel

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 90% formic acid (26.4 mL, 689 mmol) and 30% hydrogen peroxide (6.0 mL, 39.2 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-cyclopentenyl-2,4-difluorobenzene (7.064 g, 39.2 mmol) while stirring. The two-phase system was initially stirred at room temperature. After a certain period of time, a spontaneous exothermic reaction took place, and the temperature rose to about 50° C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the content of the separatory funnel was vigorously shaken. The organic layer was separated and the aqueous layer was extracted with ether. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel to give 2-(2,4-difluorophenyl)cyclopentanone (3.503 g, 17.85 mmol, 45.5% yield) as a colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.08 (1H, td, J=8.4, 6.4 Hz), 6.76-6.86 (2H, m), 3.42 (1H, dd, J=12.2, 8.9 Hz), 2.42-2.53 (2H, m), 2.28-2.39 (1H, m), 2.13-2.23 (1H, m), 1.86-2.10 (2H, m). The two-phase system was initially stirred at room temperature After a certain period of time a spontaneous exothermic reaction rose to about 50° C The reaction mixture was stirred at room temperature for 2 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the content of the separatory funnel was vigorously shaken The organic layer was separated the aqueous layer was extracted with ether The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuo the residue was purified by column chromatography on silica gel

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=265.1. washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=266.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.19-8.64 (1H, m), 7.10 (1H, td, J=8.5, 6.3 Hz), 6.78-6.92 (2H, m), 4.36-4.49 (1H, m), 2.79-2.92 (1H, m), 2.59-2.78 (2H, m), 2.08 (1H, ddd, J=9.3, 6.9, 6.7 Hz). washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=266.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.19-8.64 (1H, m), 7.10 (1H, td, J=8.5, 6.3 Hz), 6.78-6.92 (2H, m), 4.36-4.49 (1H, m), 2.79-2.92 (1H, m), 2.59-2.78 (2H, m), 2.08 (1H, ddd, J=9.3, 6.9, 6.7 Hz). washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 90% formic acid (26.4 mL, 689 mmol) and 30% hydrogen peroxide (6.0 mL, 39.2 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-cyclopentenyl-2,4-difluorobenzene (7.064 g, 39.2 mmol) under stirring. The two-phase system was initially stirred at room temperature. After a certain period of time, a spontaneous exothermic reaction took place, and the temperature rose to about 50° C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the content of the separatory funnel was vigorously shaken. The organic layer was separated and the aqueous layer was extracted with ether. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 2-(2,4-difluorophenyl)cyclopentanone (3.503 g, 17.85 mmol, 45.5% yield) as colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.08 (1H, td, J=8.4, 6.4 Hz), 6.76-6.86 (2H, m), 3.42 (1H, dd, J=12.2, 8.9 Hz), 2.42-2.53 (2H, m), 2.28-2.39 (1H, m), 2.13-2.23 (1H, m), 1.86-2.10 (2H, m). The two-phase system was initially stirred at room temperature After a certain period of time a spontaneous exothermic reaction rose to about 50° C The reaction mixture was stirred at room temperature for 2 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the content of the separatory funnel was vigorously shaken The organic layer was separated the aqueous layer was extracted with ether The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=266.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.19-8.64 (1H, m), 7.10 (1H, td, J=8.5, 6.3 Hz), 6.78-6.92 (2H, m), 4.36-4.49 (1H, m), 2.79-2.92 (1H, m), 2.59-2.78 (2H, m), 2.08 (1H, ddd, J=9.3, 6.9, 6.7 Hz). washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=266.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.19-8.64 (1H, m), 7.10 (1H, td, J=8.5, 6.3 Hz), 6.78-6.92 (2H, m), 4.36-4.49 (1H, m), 2.79-2.92 (1H, m), 2.59-2.78 (2H, m), 2.08 (1H, ddd, J=9.3, 6.9, 6.7 Hz). washed with an aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic extracts were dried over anhydrous magnesium sulfate filtered The solvent was removed in vacuum the residue was purified by column chromatography on silica gel