ETHYL 2-BROMO-(4-BROMOPHENYL)ACETATE

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

実験手順: To a solution of 2-aminoethanethiol hydrochloride (6.93 g; 61 mmol) in EtOH (400 mL) was added K2CO3 (16.86 g; 122 mmol), at RT, followed after 15 minutes by bromo-(4-bromo-phenyl)-acetic acid ethyl ester (12 mL; 61 mmol). The resulting mixture was stirred at RT for two days, subsequently, water was added and the resulting mixture was extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was recrystallized from EtOH to afford 2-(4-bromo-phenyl)-thiomorpholin-3-one (12.8 g). the resulting mixture was extracted with EtOAc The combined organic layers were dried (MgSO4) filtered concentrated in vacuo The residue was recrystallized from EtOH

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

実験手順: To a solution of 2-aminoethanethiol hydrochloride (6.93 g; 61 mmol) in EtOH (400 mL) was added K2CO3 (16.86 g; 122 mmol), at RT, followed after 15 minutes by bromo-(4-bromo-phenyl)-acetic acid ethyl ester (12 mL; 61 mmol). The resulting mixture was stirred at RT for two days, subsequently, water was added and the resulting mixture was extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was recrystallized from EtOH to afford 2-(4-bromo-phenyl)-thiomorpholin-3-one (12.8 g). the resulting mixture was extracted with EtOAc The combined organic layers were dried (MgSO4) filtered concentrated in vacuo The residue was recrystallized from EtOH

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

実験手順: To a solution of 2-aminoethanethiol hydrochloride (6.93 g; 61 mmol) in EtOH (400 mL) was added K2CO3 (16.86 g; 122 mmol), at RT, followed after 15 minutes by bromo-(4-bromo-phenyl)-acetic acid ethyl ester (12 mL; 61 mmol). The resulting mixture was stirred at RT for two days, subsequently, water was added and the resulting mixture was extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was recrystallized from EtOH to afford 2-(4-bromo-phenyl)-thiomorpholin-3-one (12.8 g). the resulting mixture was extracted with EtOAc The combined organic layers were dried (MgSO4) filtered concentrated in vacuo The residue was recrystallized from EtOH

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

実験手順: Ethyl(4-bromophenyl)[(4-hydroxyphenyl)sulfanyl]acetate was prepared according to the general method as outlined in example 1 (step 1), starting from ethyl bromo(4-bromophenyl)acetate (15 g, 45.6 mmol) and 4-mercaptophenol (5.75 g, 45.6 mmol); 15.39 g white solid. mp: 55.6° C.; Yield 92%; MS: 365.1 (M−H)−

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

実験手順: Ethyl(4-bromophenyl)[(4-hydroxyphenyl)sulfanyl]acetate was prepared according to the general method as outlined in example 1 (step 1), starting from ethyl bromo(4-bromophenyl)acetate (15 g, 45.6 mmol) and 4-mercaptophenol (5.75 g, 45.6 mmol); 15.39 g white solid. mp: 55.6° C.; Yield 92%; MS: 365.1 (M−H)−

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

実験手順: To a solution of 2-aminoethanethiol hydrochloride (6.93 g; 61 mmol) in EtOH (400 mL) was added K2CO3 (16.86 g; 122 mmol), at RT, followed after 15 minutes by bromo-(4-bromo-phenyl)-acetic acid ethyl ester (12 mL; 61 mmol). The resulting mixture was stirred at RT for two days, subsequently, water was added and the resulting mixture was extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was recrystallized from EtOH to afford 2-(4-bromo-phenyl)-thiomorpholin-3-one (12.8 g). the resulting mixture was extracted with EtOAc The combined organic layers were dried (MgSO4) filtered concentrated in vacuo The residue was recrystallized from EtOH

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

実験手順: To a solution of tert-butyl 4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (1 g, 3.35 mmol) in dichloromethane (10 mL) was added TFA (0.775 mL, 10.05 mmol). The reaction mixture was stirred at room temperature overnight, at which point the deprotection had proceeded to completion. The reaction mixture was concentrated in vacuo, dichloromethane was added, and the solution was concentrated in vacuo again. The residue was dissolved with N,N-dimethylformamide (12 mL). To this solution was added potassium carbonate (0.463 g, 3.35 mmol) and ethyl 2-bromo-2-(4-bromophenyl)acetate (1.079 g, 3.35 mmol). The reaction mixture was stirred at 40° C. for overnight, at which point the reaction had proceeded to completion. The reaction mixture was poured into water (120 mL) and was extracted with ethyl acetate (80 mL×3). The combined organic layers were dried and concentrated in vacuo. Crude ethyl 2-(4-bromo-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetate was obtained (590 mg) and was used directly in the next step. MS(ES)+ m/e 457 [M+H]+. The reaction mixture was concentrated in vacuo, dichloromethane was added the solution was concentrated in vacuo again The residue was dissolved with N,N-dimethylformamide (12 mL) The reaction mixture was stirred at 40° C. for overnight, at which was extracted with ethyl acetate (80 mL×3) The combined organic layers were dried concentrated in vacuo

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

実験手順: To a solution of 2-aminoethanethiol hydrochloride (6.93 g; 61 mmol) in EtOH (400 mL) was added K2CO3 (16.86 g; 122 mmol), at RT, followed after 15 minutes by bromo-(4-bromo-phenyl)-acetic acid ethyl ester (12 mL; 61 mmol). The resulting mixture was stirred at RT for two days, subsequently, water was added and the resulting mixture was extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was recrystallized from EtOH to afford 2-(4-bromo-phenyl)-thiomorpholin-3-one (12.8 g). the resulting mixture was extracted with EtOAc The combined organic layers were dried (MgSO4) filtered concentrated in vacuo The residue was recrystallized from EtOH

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

実験手順: To a solution of 2-aminoethanethiol hydrochloride (6.93 g; 61 mmol) in EtOH (400 mL) was added K2CO3 (16.86 g; 122 mmol), at RT, followed after 15 minutes by bromo-(4-bromo-phenyl)-acetic acid ethyl ester (12 mL; 61 mmol). The resulting mixture was stirred at RT for two days, subsequently, water was added and the resulting mixture was extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was recrystallized from EtOH to afford 2-(4-bromo-phenyl)-thiomorpholin-3-one (12.8 g). the resulting mixture was extracted with EtOAc The combined organic layers were dried (MgSO4) filtered concentrated in vacuo The residue was recrystallized from EtOH