2-(4-chlorophenyl)cyclopentan-1-one

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(4-chlorophenyl)cyclopentanone (7.80 g, 40.1 mmol) and carbonisocyanatidic chloride (7.61 g, 72.1 mmol) was stirred at 58° C. in a high-pressure vessel for 1 h. The temperature was raised to 130° C. and the reaction mixture was stirred for an additional 2 h. After cooling to rt, the reaction mixture solidified. The solid residue was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and filtered. The solvent was removed in vacuum and the oily residue was purified by column chromatography on silica gel to provide 7-(4-chlorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (5.4 g, 20.48 mmol, 51.1% yield). LC-MS (M+H)+=264.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.32 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 4.15-4.25 (1H, m), 2.56-2.93 (4H, m). After cooling to rt washed with saturated aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted twice with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered The solvent was removed in vacuum the oily residue was purified by column chromatography on silica gel

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of formic acid (60 mL, 84 mmol) and hydrogen peroxide (15 mL, 84 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-chloro-4-cyclopentenylbenzene (15 g, 84 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 1 h. The LC/MS analysis of the reaction mixture shows the disappearance of the starting material and the formation of the product. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the reaction mixture 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-(4-chlorophenyl)cyclopentanone (5.7 g, 29.3 mmol, 34.9% yield) as a colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.37 (2H, m), 7.11 (2H, d, J=8.5 Hz), 3.25 (1H, dd, J=11.6, 8.5 Hz), 2.44 (2H, d, J=6.1 Hz), 2.15-2.31 (1H, m), 1.96-2.15 (3H, m), 1.78-1.95 (1H, 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 1 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the reaction mixture 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

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(4-chlorophenyl)cyclopentanone (7.80 g, 40.1 mmol) and carbonisocyanatidic chloride (7.61 g, 72.1 mmol) was stirred at 58° C. in a high-pressure vessel for 1 h. The temperature was raised to 130° C. and the reaction mixture was stirred for an additional 2 h. After cooling to rt, the reaction mixture solidified. The solid residue was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and filtered. The solvent was removed in vacuum and the oily residue was purified by column chromatography on silica gel to provide 7-(4-chlorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (5.4 g, 20.48 mmol, 51.1% yield). LC-MS (M+H)+=264.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.32 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 4.15-4.25 (1H, m), 2.56-2.93 (4H, m). After cooling to rt washed with saturated aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted twice with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered The solvent was removed in vacuum the oily residue was purified by column chromatography on silica gel

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(4-chlorophenyl)cyclopentanone (7.80 g, 40.1 mmol) and carbonisocyanatidic chloride (7.61 g, 72.1 mmol) was stirred at 58° C. in a high-pressure vessel for 1 h. The temperature was raised to 130° C. and the reaction mixture was stirred for an additional 2 h. After cooling to rt, the reaction mixture solidified. The solid residue was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and filtered. The solvent was removed in vacuum and the oily residue was purified by column chromatography on silica gel to provide 7-(4-chlorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (5.4 g, 20.48 mmol, 51.1% yield). LC-MS (M+H)+=264.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.32 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 4.15-4.25 (1H, m), 2.56-2.93 (4H, m). After cooling to rt washed with saturated aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted twice with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered The solvent was removed in vacuum the oily residue was purified by column chromatography on silica gel

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of formic acid (60 mL, 84 mmol) and hydrogen peroxide (15 mL, 84 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-chloro-4-cyclopentenylbenzene (15 g, 84 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 1 h. The LC/MS analysis of the reaction mixture shows the disappearance of the starting material and the formation of the product. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the reaction mixture 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-(4-chlorophenyl)cyclopentanone (5.7 g, 29.3 mmol, 34.9% yield) as a colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.37 (2H, m), 7.11 (2H, d, J=8.5 Hz), 3.25 (1H, dd, J=11.6, 8.5 Hz), 2.44 (2H, d, J=6.1 Hz), 2.15-2.31 (1H, m), 1.96-2.15 (3H, m), 1.78-1.95 (1H, 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 1 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the reaction mixture 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

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(4-chlorophenyl)cyclopentanone (7.80 g, 40.1 mmol) and carbonisocyanatidic chloride (7.61 g, 72.1 mmol) was stirred at 58° C. in a high-pressure vessel for 1 h. The temperature was raised to 130° C. and the reaction mixture was stirred for an additional 2 h. After cooling to rt, the reaction mixture solidified. The solid residue was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and filtered. The solvent was removed in vacuum and the oily residue was purified by column chromatography on silica gel to provide 7-(4-chlorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (5.4 g, 20.48 mmol, 51.1% yield). LC-MS (M+H)+=264.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.32 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 4.15-4.25 (1H, m), 2.56-2.93 (4H, m). After cooling to rt washed with saturated aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted twice with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered The solvent was removed in vacuum the oily residue was purified by column chromatography on silica gel

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of formic acid (60 mL, 84 mmol) and hydrogen peroxide (15 mL, 84 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-chloro-4-cyclopentenylbenzene (15 g, 84 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 1 h. The LC/MS analysis of the reaction mixture shows the disappearance of the starting material and the formation of the product. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the reaction mixture 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-(4-chlorophenyl)cyclopentanone (5.7 g, 29.3 mmol, 34.9% yield) as a colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.37 (2H, m), 7.11 (2H, d, J=8.5 Hz), 3.25 (1H, dd, J=11.6, 8.5 Hz), 2.44 (2H, d, J=6.1 Hz), 2.15-2.31 (1H, m), 1.96-2.15 (3H, m), 1.78-1.95 (1H, 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 1 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the reaction mixture 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

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of formic acid (60 mL, 84 mmol) and hydrogen peroxide (15 mL, 84 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-chloro-4-cyclopentenylbenzene (15 g, 84 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 1 h. The LC/MS analysis of the reaction mixture shows the disappearance of the starting material and the formation of the product. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the reaction mixture 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-(4-chlorophenyl)cyclopentanone (5.7 g, 29.3 mmol, 34.9% yield) as a colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.37 (2H, m), 7.11 (2H, d, J=8.5 Hz), 3.25 (1H, dd, J=11.6, 8.5 Hz), 2.44 (2H, d, J=6.1 Hz), 2.15-2.31 (1H, m), 1.96-2.15 (3H, m), 1.78-1.95 (1H, 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 1 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the reaction mixture 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

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of formic acid (60 mL, 84 mmol) and hydrogen peroxide (15 mL, 84 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-chloro-4-cyclopentenylbenzene (15 g, 84 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 1 h. The LC/MS analysis of the reaction mixture shows the disappearance of the starting material and the formation of the product. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the reaction mixture 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-(4-chlorophenyl)cyclopentanone (5.7 g, 29.3 mmol, 34.9% yield) as a colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.37 (2H, m), 7.11 (2H, d, J=8.5 Hz), 3.25 (1H, dd, J=11.6, 8.5 Hz), 2.44 (2H, d, J=6.1 Hz), 2.15-2.31 (1H, m), 1.96-2.15 (3H, m), 1.78-1.95 (1H, 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 1 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the reaction mixture 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

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(4-chlorophenyl)cyclopentanone (7.80 g, 40.1 mmol) and carbonisocyanatidic chloride (7.61 g, 72.1 mmol) was stirred at 58° C. in a high-pressure vessel for 1 h. The temperature was raised to 130° C. and the reaction mixture was stirred for an additional 2 h. After cooling to rt, the reaction mixture solidified. The solid residue was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and filtered. The solvent was removed in vacuum and the oily residue was purified by column chromatography on silica gel to provide 7-(4-chlorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (5.4 g, 20.48 mmol, 51.1% yield). LC-MS (M+H)+=264.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.32 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 4.15-4.25 (1H, m), 2.56-2.93 (4H, m). After cooling to rt washed with saturated aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted twice with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered The solvent was removed in vacuum the oily residue was purified by column chromatography on silica gel

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of formic acid (60 mL, 84 mmol) and hydrogen peroxide (15 mL, 84 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-chloro-4-cyclopentenylbenzene (15 g, 84 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 1 h. The LC/MS analysis of the reaction mixture shows the disappearance of the starting material and the formation of the product. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the reaction mixture 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-(4-chlorophenyl)cyclopentanone (5.7 g, 29.3 mmol, 34.9% yield) as a colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.37 (2H, m), 7.11 (2H, d, J=8.5 Hz), 3.25 (1H, dd, J=11.6, 8.5 Hz), 2.44 (2H, d, J=6.1 Hz), 2.15-2.31 (1H, m), 1.96-2.15 (3H, m), 1.78-1.95 (1H, 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 1 h The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution Ether was added the reaction mixture 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

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(4-chlorophenyl)cyclopentanone (7.80 g, 40.1 mmol) and carbonisocyanatidic chloride (7.61 g, 72.1 mmol) was stirred at 58° C. in a high-pressure vessel for 1 h. The temperature was raised to 130° C. and the reaction mixture was stirred for an additional 2 h. After cooling to rt, the reaction mixture solidified. The solid residue was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and filtered. The solvent was removed in vacuum and the oily residue was purified by column chromatography on silica gel to provide 7-(4-chlorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (5.4 g, 20.48 mmol, 51.1% yield). LC-MS (M+H)+=264.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.32 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 4.15-4.25 (1H, m), 2.56-2.93 (4H, m). After cooling to rt washed with saturated aqueous solution of sodium bicarbonate The organic layer was separated the aqueous layer was extracted twice with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered The solvent was removed in vacuum the oily residue was purified by column chromatography on silica gel