1-benzylimidazolidin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 2 A mixture of 1,3-dibromo-2-methylbenzene (0.147 mL, 1.064 mmol), 1-benzylimidazolidin-2-one (75 mg, 0.426 mmol), copper (I) iodide (8.11 mg, 0.043 mmol), (+/−)-trans-1,2-diaminocyclohexane (5.1 mL, 0.043 mmol) and tripotassium phosphate (181 mg, 0.851 mmol) in dioxane (2 mL) was sonicated while bubbling with argon for 1 min. The mixture was heated in a sealed tube at 120° C. After 18.25 h, the mixture was cooled to rt, diluted with EtOAc and filtered through Celite. The filtrate was concentrated and the residue was purified by column chromatography (eluting with a gradient from 20:80 EtOAc-hexane to EtOAc) to provide 1-benzyl-3-(3-bromo-2-methylphenyl)imidazolidin-2-one as a waxy white solid (36 mg, 25%). 1H NMR (400 MHz, chloroform-d) δ 7.49 (1H, dd, J=7.9, 0.9 Hz), 7.28-7.40 (5H, m), 7.19 (1H, dd, J=7.8, 1.0 Hz), 7.08 (1H, t, J=7.9 Hz), 4.46 (2H, s), 3.64 (2H, dd, J=8.8, 6.8 Hz), 3.37 (2H, dd, J=8.8, 7.0 Hz), 2.36 (3H, s). Mass spectrum m/z 346.8 (M+H)+. was sonicated while bubbling with argon for 1 min the mixture was cooled to rt diluted with EtOAc filtered through Celite The filtrate was concentrated the residue was purified by column chromatography ( eluting with a gradient from 20:80 EtOAc-hexane to EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1 A solution of imidazolidin-2-one (500 mg, 5.81 mmol) in DMF (30 mL) was stirred on ice and treated with sodium hydride, 60% oil dispersion (264 mg, 6.60 mmol). The mixture was stirred at rt for 50 min, then was treated with (bromomethyl)benzene (0.691 mL, 5.81 mmol). After 2 h, the mixture was poured into water and extracted three times with EtOAc. The combined organic layers were dried and concentrated, and the residue was purified by column chromatography (eluting with EtOAc) to provide 1-benzylimidazolidin-2-one as a white solid (160 mg, 16%). 1H NMR (400 MHz, chloroform-d) δ 7.22-7.39 (5H, m), 4.53 (1H, br. s.), 4.37 (2H, s), 3.25-3.46 (4H, m). After 2 h extracted three times with EtOAc The combined organic layers were dried concentrated the residue was purified by column chromatography (eluting with EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1 A solution of imidazolidin-2-one (500 mg, 5.81 mmol) in DMF (30 mL) was stirred on ice and treated with sodium hydride, 60% oil dispersion (264 mg, 6.60 mmol). The mixture was stirred at rt for 50 min, then was treated with (bromomethyl)benzene (0.691 mL, 5.81 mmol). After 2 h, the mixture was poured into water and extracted three times with EtOAc. The combined organic layers were dried and concentrated, and the residue was purified by column chromatography (eluting with EtOAc) to provide 1-benzylimidazolidin-2-one as a white solid (160 mg, 16%). 1H NMR (400 MHz, chloroform-d) δ 7.22-7.39 (5H, m), 4.53 (1H, br. s.), 4.37 (2H, s), 3.25-3.46 (4H, m). After 2 h extracted three times with EtOAc The combined organic layers were dried concentrated the residue was purified by column chromatography (eluting with EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-benzylimidazolidin-2-one (3.5 g, 19.9 mmol) in DMF (50 ml) at 0° C. were added lithium tert-butoxide (1.9 g, 23.8 mmol) and tert-butyl bromoacetate (3.2 ml, 21.8 mmol). After stirring the mixture at room temperature overnight, the reaction mixture was poured into water (100 ml) and the mixture was extracted with ethyl acetate. The organic phase was washed with water, 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution and brine. The organic solution was dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The crystalline residue was washed with n-hexane, and dried to give tert-butyl 2-(2-oxo-3-benzylimidazolidinyl)acetate (5.08 g). the mixture was extracted with ethyl acetate The organic phase was washed with water, 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution and brine The organic solution was dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure The crystalline residue was washed with n-hexane dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzylethylenediamine (6.0 g, 40 mmol) in toluene (50 ml) at 0° C. was added 1,1′-carbonylbis-1H-imidazole (7.8 g, 48 mmol). After stirring the mixture at room temperature overnight, the reaction mixture was washed with water, 5% aqueous citric acid solution and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was recrystallized with warm ethyl acetate and filtered off to give 1-benzylimidazolidin-2-one (3.47 g). the reaction mixture was washed with water, 5% aqueous citric acid solution and brine The organic phase was dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure The residue was recrystallized with warm ethyl acetate filtered off

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-benzylimidazolidin-2-one (3.5 g, 19.9 mmol) in DMF (50 ml) at 0° C. were added lithium tert-butoxide (1.9 g, 23.8 mmol) and tert-butyl bromoacetate (3.2 ml, 21.8 mmol). After stirring the mixture at room temperature overnight, the reaction mixture was poured into water (100 ml) and the mixture was extracted with ethyl acetate. The organic phase was washed with water, 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution and brine. The organic solution was dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The crystalline residue was washed with n-hexane, and dried to give tert-butyl 2-(2-oxo-3-benzylimidazolidinyl)acetate (5.08 g). the mixture was extracted with ethyl acetate The organic phase was washed with water, 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution and brine The organic solution was dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure The crystalline residue was washed with n-hexane dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzylethylenediamine (6.0 g, 40 mmol) in toluene (50 ml) at 0° C. was added 1,1′-carbonylbis-1H-imidazole (7.8 g, 48 mmol). After stirring the mixture at room temperature overnight, the reaction mixture was washed with water, 5% aqueous citric acid solution and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was recrystallized with warm ethyl acetate and filtered off to give 1-benzylimidazolidin-2-one (3.47 g). the reaction mixture was washed with water, 5% aqueous citric acid solution and brine The organic phase was dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure The residue was recrystallized with warm ethyl acetate filtered off