2-chloroethylsulfinylbenzene

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

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

Procedure: A mixture of 20.0 g (0.106 mole) of [(2-chloroethyl)sulfinyl]benzene, 30.0 g (0.259 mole) of N,N-diethylethylenediamine and excess sodium carbonate in 600 ml of acetonitrile was refluxed for 16 hr. The reaction mixture solution was filtered, and the solvent was removed in vacuo. The residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over sodium sulfate and the solvent was removed in vacuo to give an oil. This was dissolved in methanol, and a solution of 2 equivalents of maleic acid in methanol was added. Diethyl ether was added and a whie solid precipitated to give 26.7 g (50.3%) of title compound, a white crystalline solid, mp 111°-112.5° C. was refluxed for 16 hr The reaction mixture solution was filtered the solvent was removed in vacuo The residue was partitioned between methylene chloride and dilute sodium hydroxide The methylene chloride solution was dried over sodium sulfate the solvent was removed in vacuo to give an oil a whie solid precipitated

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

Procedure: tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.170 g, 0.594 mmol) and 2-chloroethyl phenyl sulfoxide (0.225 g, 1.20 mmol, 2.0 equiv.) was dissolved in DMF (10 mL) at rt. NaH (0.100 mg, 2.5 mmol, 4.21 equiv., 60% dispersion) was added, then the reaction mixture was stirred for 3 h. The reaction was quenched with a saturated aqueous NH4Cl solution and partitioned between water and CH2Cl2. The aqueous layer was extracted with CH2Cl2 (3×). The combined organic layers were concentrated and the residue was dissolved in EtOAc, dried over MgSO4, filtered, and concentrated. The crude product was chromatographed (Biotage 12 m SiO2 column, eluted with a 20% to 30% EtOAc in hexane gradient) to give tert-butyl 6-[2-(phenylsulfinyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate. The reaction was quenched with a saturated aqueous NH4Cl solution partitioned between water and CH2Cl2 The aqueous layer was extracted with CH2Cl2 (3×) The combined organic layers were concentrated the residue was dissolved in EtOAc dried over MgSO4 filtered concentrated The crude product was chromatographed (Biotage 12 m SiO2 column eluted with a 20% to 30% EtOAc in hexane gradient)

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

Procedure: 1-(2-Phenylsulfinylethyl)-4-piperidone is prepared from 4-piperidone and 1-chloro-2-phenylsulfinylethane essentially as described above in Example 38, Scheme C, step a.

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

Procedure: 1-(2-Phenylsulfinylethyl)-4-piperidone is prepared from 4-piperidone and 1-chloro-2-phenylsulfinylethane essentially as described above in Example 38, Scheme C, step a.

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

Procedure: A mixture of 20.0 g (0.106 mole) of [(2-chloroethyl)sulfinyl]benzene, 30.0 g (0.259 mole) of N,N-diethylethylenediamine and excess sodium carbonate in 600 ml of acetonitrile was refluxed for 16 hr. The reaction mixture solution was filtered, and the solvent was removed in vacuo. The residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over sodium sulfate and the solvent was removed in vacuo to give an oil. This was dissolved in methanol, and a solution of 2 equivalents of maleic acid in methanol was added. Diethyl ether was added and a whie solid precipitated to give 26.7 g (50.3%) of title compound, a white crystalline solid, mp 111°-112.5° C. was refluxed for 16 hr The reaction mixture solution was filtered the solvent was removed in vacuo The residue was partitioned between methylene chloride and dilute sodium hydroxide The methylene chloride solution was dried over sodium sulfate the solvent was removed in vacuo to give an oil a whie solid precipitated

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

Procedure: A mixture of 20.0 g (0.106 mole) of [(2-chloroethyl)sulfinyl]benzene, 30.0 g (0.259 mole) of N,N-diethylethylenediamine and excess sodium carbonate in 600 ml of acetonitrile was refluxed for 16 hr. The reaction mixture solution was filtered, and the solvent was removed in vacuo. The residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over sodium sulfate and the solvent was removed in vacuo to give an oil. This was dissolved in methanol, and a solution of 2 equivalents of maleic acid in methanol was added. Diethyl ether was added and a whie solid precipitated to give 26.7 g (50.3%) of title compound, a white crystalline solid, mp 111°-112.5° C. was refluxed for 16 hr The reaction mixture solution was filtered the solvent was removed in vacuo The residue was partitioned between methylene chloride and dilute sodium hydroxide The methylene chloride solution was dried over sodium sulfate the solvent was removed in vacuo to give an oil a whie solid precipitated

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

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

Procedure: tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.170 g, 0.594 mmol) and 2-chloroethyl phenyl sulfoxide (0.225 g, 1.20 mmol, 2.0 equiv.) was dissolved in DMF (10 mL) at rt. NaH (0.100 mg, 2.5 mmol, 4.21 equiv., 60% dispersion) was added, then the reaction mixture was stirred for 3 h. The reaction was quenched with a saturated aqueous NH4Cl solution and partitioned between water and CH2C2. The aqueous layer was extracted with CH2Cl2 (3×). The combined organic layers were concentrated and the residue was dissolved in EtOAc, dried over MgSO4, filtered, and concentrated. The crude product was chromatographed (Biotage 12 m SiO2 column, eluted with a 20% to 30% EtOAc in hexane gradient) to give tert-butyl 6-[2-(phenylsulfinyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate. The reaction was quenched with a saturated aqueous NH4Cl solution partitioned between water and CH2C2 The aqueous layer was extracted with CH2Cl2 (3×) The combined organic layers were concentrated the residue was dissolved in EtOAc dried over MgSO4 filtered concentrated The crude product was chromatographed (Biotage 12 m SiO2 column eluted with a 20% to 30% EtOAc in hexane gradient)

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

Procedure: tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.170 g, 0.594 mmol) and 2-chloroethyl phenyl sulfoxide (0.225 g, 1.20 mmol, 2.0 equiv.) was dissolved in DMF (10 mL) at rt. NaH (0.100 mg, 2.5 mmol, 4.21 equiv., 60% dispersion) was added, then the reaction mixture was stirred for 3 h. The reaction was quenched with a saturated aqueous NH4Cl solution and partitioned between water and CH2Cl2. The aqueous layer was extracted with CH2Cl2 (3×). The combined organic layers were concentrated and the residue was dissolved in EtOAc, dried over MgSO4, filtered, and concentrated. The crude product was chromatographed (Biotage 12m SiO2 column, eluted with a 20% to 30% EtOAc in hexane gradient) to give tert-butyl 6-[2-(phenylsulfinyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate. The reaction was quenched with a saturated aqueous NH4Cl solution partitioned between water and CH2Cl2 The aqueous layer was extracted with CH2Cl2 (3×) The combined organic layers were concentrated the residue was dissolved in EtOAc dried over MgSO4 filtered concentrated The crude product was chromatographed (Biotage 12m SiO2 column eluted with a 20% to 30% EtOAc in hexane gradient)

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

Procedure: tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.170 g, 0.594 mmol) and 2-chloroethyl phenyl sulfoxide (0.225 g, 1.20 mmol, 2.0 equiv.) was dissolved in DMF (10 mL) at rt. NaH (0.100 mg, 2.5 mmol, 4.21 equiv., 60% dispersion) was added, then the reaction mixture was stirred for 3 h. The reaction was quenched with a saturated aqueous NH4Cl solution and partitioned between water and CH2Cl2. The aqueous layer was extracted with CH2Cl2 (3×). The combined organic layers were concentrated and the residue was dissolved in EtOAc, dried over MgSO4, filtered, and concentrated. The crude product was chromatographed (Biotage 12 m SiO2 column, eluted with a 20% to 30% EtOAc in hexane gradient) to give tert-butyl 6-[2-(phenylsulfinyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate. The reaction was quenched with a saturated aqueous NH4Cl solution partitioned between water and CH2Cl2 The aqueous layer was extracted with CH2Cl2 (3×) The combined organic layers were concentrated the residue was dissolved in EtOAc dried over MgSO4 filtered concentrated The crude product was chromatographed (Biotage 12 m SiO2 column eluted with a 20% to 30% EtOAc in hexane gradient)

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

Procedure: tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.170 g, 0.594 mmol) and 2-chloroethyl phenyl sulfoxide (0.225 g, 1.20 mmol, 2.0 equiv.) was dissolved in DMF (10 mL) at rt. NaH (0.100 mg, 2.5 mmol, 4.21 equiv., 60% dispersion) was added, then the reaction mixture was stirred for 3 h. The reaction was quenched with a saturated aqueous NH4Cl solution and partitioned between water and CH2Cl2. The aqueous layer was extracted with CH2Cl2 (3×). The combined organic layers were concentrated and the residue was dissolved in EtOAc, dried over MgSO4, filtered, and concentrated. The crude product was chromatographed (Biotage 12 m SiO2 column, eluted with a 20% to 30% EtOAc in hexane gradient) to give tert-butyl 6-[2-(phenylsulfinyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate. The reaction was quenched with a saturated aqueous NH4Cl solution partitioned between water and CH2Cl2 The aqueous layer was extracted with CH2Cl2 (3×) The combined organic layers were concentrated the residue was dissolved in EtOAc dried over MgSO4 filtered concentrated The crude product was chromatographed (Biotage 12 m SiO2 column eluted with a 20% to 30% EtOAc in hexane gradient)