tert-butyl 4-(2-methylsulfonylethyl)piperazine-1-carboxylate

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:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 1,1-dimethylethyl 4-[2-(methylsulfonyl)ethyl]-1-piperazinecarboxylate (106 g, 360 mmol) in MeOH (500 mL) was added HCl/MeOH (5M, 1000 mL, 5000 mmol), and the mixture was heated at 50° C. for 1 h before evaporating most of the solvent. The residue was filtered and washed with MeOH to give the desired product as HCl salt (90.3 g, 95% yield). 1H NMR (400 MHz, D2O) δ ppm 3.30-3.72 (m, 12H), 3.09 (s, 3H). before evaporating most of the solvent The residue was filtered washed with MeOH

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

実験手順: To a solution of 1,1-dimethylethyl 1-piperazinecarboxylate (72.8 g, 390 mmol) in acetonitrile (1.4 L) was added methyl vinyl sulfone (50 g, 470 mmol) and Na2CO3 (124 g, 1170 mmol) and the mixture was refluxed overnight. Then the mixture was cooled to rt, and poured into H2O and extracted with EtOAc. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure to give the title compound (106 g, 93% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.41-1.57 (m, 9H), 2.39-2.51 (m, 4H), 2.88 (t, J=8.4 Hz, 2H), 3.02 (s, 3H), 3.14 (t, J=8.4 Hz, 2H), 3.35-3.50 (m, 4H). the mixture was refluxed overnight extracted with EtOAc The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure

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

実験手順: Hydrochloric acid (42 mL, 168 mmol, 4 M in 1,4-dioxane) was added to a cooled solution of 1-tert-butyloxycarbonyl-4-(2-methanesulfonylethyl)piperazine (2.29 g, 7.8 mmol) in 1,4-dioxane (42 mL). The mixture was stirred at room temperature overnight then concentrated to give 1-(2-methanesulfonylethyl)piperazine dihydrochloride as a white solid (2.05 g). then concentrated

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

実験手順: Methyl vinyl sulfone (1.8 mL, 20.1 mmol) was added to a solution of 1-(tert-butyloxycarbonyl)piperazine (1.50 g, 8 mmol) in methanol (84 mL). The reaction mixture was stirred at room temperature for 4 h and concentrated to a white solid. Purification of the solid by flash column chromatography (silica gel, eluting with 1-5% methanol in methylene chloride) gave 1-tert-butyloxycarbonyl-4-(2-methanesulfonylethyl)piperazine as a white solid (2.29 g, 95%). concentrated to a white solid Purification of the solid by flash column chromatography (silica gel, eluting with 1-5% methanol in methylene chloride)

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

実験手順: Methyl vinyl sulfone (1.8 mL, 20.1 mmol) was added to a solution of 1-(tert-butyloxycarbonyl)piperazine (1.50 g, 8 mmol) in methanol (84 mL). The reaction mixture was stirred at room temperature for 4 h and concentrated to a white solid. Purification of the solid by flash column chromatography (silica gel, eluting with 1-5% methanol in methylene chloride) gave 1-tert-butyloxycarbonyl-4-(2-methanesulfonylethyl)piperazine as a white solid (2.29 g, 95%). concentrated to a white solid Purification of the solid by flash column chromatography (silica gel, eluting with 1-5% methanol in methylene chloride)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 1,1-dimethylethyl 4-[2-(methylsulfonyl)ethyl]-1-piperazinecarboxylate (106 g, 360 mmol) in MeOH (500 mL) was added HCl/MeOH (5M, 1000 mL, 5000 mmol), and the mixture was heated at 50° C. for 1 h before evaporating most of the solvent. The residue was filtered and washed with MeOH to give the desired product as HCl salt (90.3 g, 95% yield). 1H NMR (400 MHz, D2O) δ ppm 3.30-3.72 (m, 12H), 3.09 (s, 3H). before evaporating most of the solvent The residue was filtered washed with MeOH

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

実験手順: To a solution of 1,1-dimethylethyl 1-piperazinecarboxylate (72.8 g, 390 mmol) in acetonitrile (1.4 L) was added methyl vinyl sulfone (50 g, 470 mmol) and Na2CO3 (124 g, 1170 mmol) and the mixture was refluxed overnight. Then the mixture was cooled to rt, and poured into H2O and extracted with EtOAc. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure to give the title compound (106 g, 93% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.41-1.57 (m, 9H), 2.39-2.51 (m, 4H), 2.88 (t, J=8.4 Hz, 2H), 3.02 (s, 3H), 3.14 (t, J=8.4 Hz, 2H), 3.35-3.50 (m, 4H). the mixture was refluxed overnight extracted with EtOAc The organic layer was dried over Na2SO4 the solvent was removed under reduced pressure

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: Hydrochloric acid (42 mL, 168 mmol, 4 M in 1,4-dioxane) was added to a cooled solution of 1-tert-butyloxycarbonyl-4-(2-methanesulfonylethyl)piperazine (2.29 g, 7.8 mmol) in 1,4-dioxane (42 mL). The mixture was stirred at room temperature overnight then concentrated to give 1-(2-methanesulfonylethyl)piperazine dihydrochloride as a white solid (2.05 g). then concentrated