2-chloroethylsulfonylbenzene

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:

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

実験手順: A mixture of 28.2 g (0.138 mole) of [(2-chloroethyl)sulfonyl]benzene and 20.0 g (0.139 mole) of 4-(N,N-diethylamino)-1-butanamine in 700 ml of acetonitrile was stirred at room temperature for 16 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over magnesium sulfate, and the solvent was removed in vacuo. The residue was dissolved in methanol, a solution of 25.0 g (0.278 mole) of oxalic acid was added and a precipitate was collected to give 47.69 g (68.9%) of title compound, a white crystalline solid, mp 158°-165° C. with decomposition. The solvent was removed in vacuo the residue was partitioned between methylene chloride and dilute sodium hydroxide The methylene chloride solution was dried over magnesium sulfate the solvent was removed in vacuo The residue was dissolved in methanol a precipitate was collected

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

実験手順: A mixture of 20.06 g (0.098 mole) of [(2-chloroethyl)sulfonyl]benzene 15.44 g (0.109 mole) of N-(2-aminoethyl)homopiperidine, and 15.0 g (0.149 mole) of triethylamine in 800 ml of acetonitrile was stirred at room temperature for 18 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and water. The methylene chloride solution was dried over magnesuim sulfate, and the solvent waas removed in vacuo to give an oil. This was dissolved in methanol, and the solution was treated with a solution of 2 equivalents of maleic acid (25.52 g, 0.22 mole) in methanol. A white solid precipitated at room temperature to give 32.3 g (60.7%) of title compound as a white solid; mp 144°-146° C. The solvent was removed in vacuo the residue was partitioned between methylene chloride and water The methylene chloride solution was dried over magnesuim sulfate the solvent waas removed in vacuo to give an oil A white solid precipitated at room temperature

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

実験手順: A mixture of 40.94 g (0.20 mole) of [(2-chloroethyl)sulfonyl]benzene, 27.85 g (0.217 mole) of N-(2-aminoethyl)piperidine and 28.0 g (0.277 mole) of triethylamine in 800 ml of acetonitrile was stirred at room temperature overnight. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over magnesium sulfate, and the solvent was removed in vacuo. The residue was dissolved in methanol, a solution of 2 equivalents of maleic acid in methanol was added, and the product crystallized from the solution at room temperatue to give 64.35 g (60.78%) of title compound as a white crystalline solid, mp 154°-155.5° C. The solvent was removed in vacuo the residue was partitioned between methylene chloride and dilute sodium hydroxide The methylene chloride solution was dried over magnesium sulfate the solvent was removed in vacuo The residue was dissolved in methanol the product crystallized from the solution at room temperatue

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

実験手順: (β-chloroethylsulfonyl)benzene (4.09 g, 20 mmol) was added to 20 g of toluene, to this solution were added 3.00 g of 49% aqueous potassium carbonate solution (potassium carbonate 10.6 mmol) and 113 mg (1.0 mmol) or diisopropylethylamine, and the mixture was stirred for 4 hours at 40° C. Then, 10 g of water was added and the mixture was separated to an organic phase and aqueous phase. This aqueous phase was extracted by chloroform, and the resulted organic phase was combined with the previous organic phase, dried over magnesium sulfate, the solvents were distilled off, to obtain 2.76 g (yield 82.1%) of phenylvinylsulfone. the mixture was separated to an organic phase and aqueous phase This aqueous phase was extracted by chloroform dried over magnesium sulfate the solvents were distilled off

反応条件: temp:42.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (β-chloroethylsulfonyl)benzene (40.9 g, 200 mmol) was dissolved in 100 g of toluene, to this solution were added 30.7 g of 49% aqueous potassium carbonate solution (potassium carbonate 109 mmol) and 1.01 g (10 mmol) of triethylamine, and the mixture was stirred for 3 hours at from 40 to 45° C. Then, the mixture was washed with 70 g of water once, with 35 g of 5% aqueous sulfuric acid solution once and further with 35 g of water once, and the solvents were distilled off to obtain 33.1 g (yield 98.4%) of phenylvinylsulfone. Then, the mixture was washed with 70 g of water once with 35 g of 5% aqueous sulfuric acid solution once and further with 35 g of water once, and the solvents were distilled off

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

実験手順: tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.111 g, 0.388 mmol) was dissolved in CH2Cl2 (10 mL) and this solution was added to a mixture of 50% aqueous KOH (5 mL) and tetrabutylammonium hydrogen sulfate (0.100 g). The biphasic mixture was stirred vigorously at rt. 2-Chloroethyl phenyl sulfone (0.318 g, 1.55 mmol) was added, then the reaction mixture was stirred for 4 h. The organic phase was separated and the aqueous phase was extracted with CH2Cl2. The combined organic layers was concentrated. The crude product was chromatographed (Biotage 40s SiO2 column, eluted with a 10% to 40% EtOAc in hexane gradient) to give tert-butyl 6-[2-(phenylsulfonyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.154 g) in 87% as a clear solid. 1H NMR (300 MHz, CDCl3) δ 1.48, 2.87-2.93, 3.38-3.42, 3.63, 3.69, 4.52, 7.04-7.17, 7.42, 7.53-7.59, 7.63-7.70, 7.88. the reaction mixture was stirred for 4 h The organic phase was separated the aqueous phase was extracted with CH2Cl2 The combined organic layers was concentrated The crude product was chromatographed (Biotage 40s SiO2 column eluted with a 10% to 40% EtOAc in hexane gradient)

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

実験手順: tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.111 g, 0.388 mmol) was dissolved in CH2Cl2 (10 mL) and this solution was added to a mixture of 50% aqueous KOH (5 mL) and tetrabutylammonium hydrogen sulfate (0.100 g). The biphasic mixture was stirred vigorously at rt. 2-Chloroethyl phenyl sulfone (0.318 g, 1.55 mmol) was added, then the reaction mixture was stirred for 4 h. The organic phase was separated and the aqueous phase was extracted with CH2Cl2. The combined organic layers was concentrated. The crude product was chromatographed (Biotage 40s SiO2 column, eluted with a 10% to 40% EtOAc in hexane gradient) to give tert-butyl 6-[2-(phenylsulfonyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.154 g) in 87% as a clear solid. 1H NMR (300 MHz, CDCl3) δ 1.48, 2.87-2.93, 3.38-3.42, 3.63, 3.69, 4.52, 7.04-7.17, 7.42, 7.53-7.59, 7.63-7.70, 7.88. the reaction mixture was stirred for 4 h The organic phase was separated the aqueous phase was extracted with CH2Cl2 The combined organic layers was concentrated The crude product was chromatographed (Biotage 40s SiO2 column eluted with a 10% to 40% EtOAc in hexane gradient)

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

実験手順: A mixture of 51.4 g (0.253 mole) of 2-chloroethyl phenyl sulfone, 50.2 g (0.417 mole) of 3-ethoxy-1-propanamine, and 33.0 g (0.327 mole) of triethylamine in 400 ml of acetonitrile was stirred at room temperature for 20 hr. The solvent was removed in vacuo and the residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride phase was dried over magnesium sulfate, and the solvent was removed in vacuo to give an oil. This was dissolved in methanol, an excess of ethereal hydrogen chloride was added and ether was added. A precipitate was collected to give 49.2 g (63.2%) of white crystalline solid, m.p. 169°-170° C. The solvent was removed in vacuo the residue was partitioned between methylene chloride and dilute sodium hydroxide The methylene chloride phase was dried over magnesium sulfate the solvent was removed in vacuo to give an oil A precipitate was collected

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

実験手順: A mixture of 51.4 g (0.253 mole) of 2-chloroethyl phenyl sulfone, 50.2 g (0.417 mole) of 3-ethoxy-1-propanamine, and 33.0 g (0.327 mole) of triethylamine in 400 ml of acetonitrile was stirred at room temperature for 20 hr. The solvent was removed in vacuo and the residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride phase was dried over magnesium sulfate, and the solvent was removed in vacuo to give an oil. This was dissolved in methanol, an excess of ethereal hydrogen chloride was added and ether was added. A precipitate was collected to give 49.2 g (63.2%) of white crystalline solid, m.p. 169°-170° C. The solvent was removed in vacuo the residue was partitioned between methylene chloride and dilute sodium hydroxide The methylene chloride phase was dried over magnesium sulfate the solvent was removed in vacuo to give an oil A precipitate was collected