2-(4-chlorophenyl)sulfanylethanamine

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

Procedure: To a solution of 2-[(4-chlorophenyl)sulfanyl]ethanamine (12.2 g, 542 mmol) in DMF (350 ml) was added sequentially 4-(methoxycarbonyl)cyclohexanecarboxylic acid (cis/trans mixture), EDC (11.4 g, 59.7 mmol) and HOAt (1.48 g, 10.9 mmol) at room temperature followed by Et3N (17.39 ml, 125 mmol). The reaction was stirred overnight at ambient temperature, diluted with water and extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and conc. The residue was purified by silica gel flash chromatography (0-70% EtOAc in heptane) to afford the product. LCMS: M+H=356.1. extracted with EtOAc The combined organic layers were dried (Na2SO4) filtered conc. The residue was purified by silica gel flash chromatography (0-70% EtOAc in heptane) to afford the product

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

Procedure: To a solution of 2-[(4-chlorophenyl)sulfanyl]ethanamine (12.2 g, 542 mmol) in DMF (350 ml) was added sequentially 4-(methoxycarbonyl)cyclohexanecarboxylic acid (cis/trans mixture), EDC (11.4 g, 59.7 mmol) and HOAt (1.48 g, 10.9 mmol) at room temperature followed by Et3N (17.39 ml, 125 mmol). The reaction was stirred overnight at ambient temperature, diluted with water and extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and conc. The residue was purified by silica gel flash chromatography (0-70% EtOAc in heptane) to afford the product. LCMS: M+H=356.1. extracted with EtOAc The combined organic layers were dried (Na2SO4) filtered conc. The residue was purified by silica gel flash chromatography (0-70% EtOAc in heptane) to afford the product

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

Procedure: To a solution of 2-[(4-chlorophenyl)sulfanyl]ethanamine (15.32 g, 82 mmol, prepared from 4-chlorothiophenol and 2-chloroethylamine as described before) in DMF (247 ml) was added sequentially tetrahydro-2H-pyran-4-carboxylic acid (9.66 g, 74.2 mmol), EDC (15.65 g, 82 mmol) and HOAt (2.021 g, 14.85 mmol) and the reaction mixture was stirred at RT overnight. The reaction mixture was diluted with EtOAc, washed with 1N HCl, aq NaHCO3, 3M LiCl, dried over sodium sulfate, concentrated in vacuo and purified by flash chromatography (silica 1 kg, 50 to 100% EtOAc in hexane), to give N-{2-[(4-chlorophenyl)sulfanyl]ethyl}tetrahydro-2H-pyran-4-carboxamide (1825 g). MS: M+H=300. H1NMR (400 MHz, CDCl3) δ: 7.31 (d, J=9.9 Hz, 2H), 7.26 (d, J=9.9 Hz, 2H), 5.82 (br s, 1 H), 4.40-3.96 (m, 2H), 3.46 (dt, J=7.0, 7.0 Hz, 2H), 3.45-3.36 (m, 2H), 3.05 (t, J=7.0 Hz, 2 H), 2.34-2.26 (m, 1H), 1.82-1.65 (m, 4H). washed with 1N HCl, aq NaHCO3, 3M LiCl dried over sodium sulfate concentrated in vacuo purified by flash chromatography (silica 1 kg, 50 to 100% EtOAc in hexane)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium metal (22.5 mg, 0.98 mmol) in ethanol (2.0 mL) was treated with 2-bromoethylamine hydrobromide (100.0 mg, 0.49 mmol) and 4-chlorobenzenethiol (71.0 mg, 0.49 mmol), heated to 75° C. for 18 hours, and concentrated. The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) and the organic phase was dried (MgSO4), filtered, and concentrated to provide the desired product. MS (DCI) m/e 188 (M+H)+. concentrated The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) the organic phase was dried (MgSO4) filtered concentrated

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium metal (22.5 mg, 0.98 mmol) in ethanol (2.0 mL) was treated with 2-bromoethylamine hydrobromide (100.0 mg, 0.49 mmol) and 4-chlorobenzenethiol (71.0 mg, 0.49 mmol), heated to 75° C. for 18 hours, and concentrated. The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) and the organic phase was dried (MgSO4), filtered, and concentrated to provide the desired product. MS (DCI) m/e 188 (M+H)+. concentrated The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) the organic phase was dried (MgSO4) filtered concentrated

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium metal (22.5 mg, 0.98 mmol) in ethanol (2.0 mL) was treated with 2-bromoethylamine hydrobromide (100.0 mg, 0.49 mmol) and 4-chlorobenzenethiol (71.0 mg, 0.49 mmol), heated to 75° C. for 18 hours, and concentrated. The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) and the organic phase was dried (MgSO4), filtered, and concentrated to provide the desired product. MS (DCI) m/e 188 (M+H)+. concentrated The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) the organic phase was dried (MgSO4) filtered concentrated

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium metal (22.5 mg, 0.98 mmol) in ethanol (2.0 mL) was treated with 2-bromoethylamine hydrobromide (100.0 mg, 0.49 mmol) and 4-chlorobenzenethiol (71.0 mg, 0.49 mmol), heated to 75° C. for 18 hours, and concentrated. The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) and the organic phase was dried (MgSO4), filtered, and concentrated to provide the desired product. MS (DCI) m/e 188 (M+H)+. concentrated The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) the organic phase was dried (MgSO4) filtered concentrated

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium metal (22.5 mg, 0.98 mmol) in ethanol (2.0 mL) was treated with 2-bromoethylamine hydrobromide (100.0 mg, 0.49 mmol) and 4-chlorobenzenethiol (71.0 mg, 0.49 mmol), heated to 75° C. for 18 hours, and concentrated. The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) and the organic phase was dried (MgSO4), filtered, and concentrated to provide the desired product. MS (DCI) m/e 188 (M+H)+. concentrated The concentrate was partitioned between water (2.0 mL) and diethyl ether (5.0 mL) the organic phase was dried (MgSO4) filtered concentrated

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

Procedure: To a solution of 2-[(4-chlorophenyl)sulfanyl]ethanamine (15.32 g, 82 mmol, prepared from 4-chlorothiophenol and 2-chloroethylamine) in DMF (247 ml) was added sequentially tetrahydro-2H-pyran-4-carboxylic acid (9.66 g, 74.2 mmol), EDC (15.65 g, 82 mmol) and HOAt (2.021 g, 14.85 mmol) and the reaction mixture was stirred at RT overnight. The reaction mixture was diluted with EtOAc, washed with 1N HCl, aq NaHCO3, 3M LiCl, dried over sodium sulfate, concentrated in vacuo and purified by flash chromatography (silica 1 kg, 50 to 100% EtOAc in hexane), to give N-{2-[(4-chlorophenyl)sulfanyl]ethyl}tetrahydro-2H-pyran-4-carboxamide (18.25 g). MS: M+H=300. H1NMR (400 MHz, CDCl3) δ: 7.31 (d, J=9.9 Hz, 2H), 7.26 (d, J=9.9 Hz, 2H), 5.82 (br s, 1H), 4.40-3.96 (m, 2H), 3.46 (dt, J=7 Hz, 7 Hz, 2H), 3.45-3.36 (m, 2H), 3.05 (t, J=7 Hz, 2H), 2.34-2.26 (m, 1H), 1.82-1.65 (m, 4H). washed with 1N HCl, aq NaHCO3, 3M LiCl dried over sodium sulfate concentrated in vacuo purified by flash chromatography (silica 1 kg, 50 to 100% EtOAc in hexane)

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

Procedure: To a solution of 2-[(4-chlorophenyl)sulfanyl]ethanamine (12.2 g, 542 mmol) in DMF (350 ml) was added sequentially 4-(methoxycarbonyl)cyclohexanecarboxylic acid (cis/trans mixture), EDC (11.4 g, 59.7 mmol) and HOAt (1.48 g, 10.9 mmol) at room temperature followed by Et3N (17.39 ml, 125 mmol). The reaction was stirred overnight at ambient temperature, diluted with water and extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and conc. The residue was purified by silica gel flash chromatography (0-70% EtOAc in heptane) to afford the product. LCMS: M+H=356.1. extracted with EtOAc The combined organic layers were dried (Na2SO4) filtered conc. The residue was purified by silica gel flash chromatography (0-70% EtOAc in heptane) to afford the product

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

Procedure: To a solution of 2-[(4-chlorophenyl)sulfanyl]ethanamine (15.32 g, 82 mmol, prepared from 4-chlorothiophenol and 2-chloroethylamine as described before) in DMF (247 ml) was added sequentially tetrahydro-2H-pyran-4-carboxylic acid (9.66 g, 74.2 mmol), EDC (15.65 g, 82 mmol) and HOAt (2.021 g, 14.85 mmol) and the reaction mixture was stirred at RT overnight. The reaction mixture was diluted with EtOAc, washed with 1N HCl, aq NaHCO3, 3M LiCl, dried over sodium sulfate, concentrated in vacuo and purified by flash chromatography (silica 1 kg, 50 to 100% EtOAc in hexane), to give N-{2-[(4-chlorophenyl)sulfanyl]ethyl}tetrahydro-2H-pyran-4-carboxamide (1825 g). MS: M+H=300. H1NMR (400 MHz, CDCl3) δ: 7.31 (d, J=9.9 Hz, 2H), 7.26 (d, J=9.9 Hz, 2H), 5.82 (br s, 1 H), 4.40-3.96 (m, 2H), 3.46 (dt, J=7.0, 7.0 Hz, 2H), 3.45-3.36 (m, 2H), 3.05 (t, J=7.0 Hz, 2 H), 2.34-2.26 (m, 1H), 1.82-1.65 (m, 4H). washed with 1N HCl, aq NaHCO3, 3M LiCl dried over sodium sulfate concentrated in vacuo purified by flash chromatography (silica 1 kg, 50 to 100% EtOAc in hexane)