1-[(E)-3-bromoprop-1-enyl]-2-chlorobenzene

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

Procedure: To an oven-dried, 100 mL, three-necked round-bottomed flask equipped with a stir bar, two septa and a nitrogen gas inlet adaptor, was added 4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (1.0 g, 4.8 mmol) and K2CO3 (2.69 g, 19.2 mmol). The flask was evaporated and refilled with nitrogen three times, then MeCN (60 mL) was added. (E)-1-(3-bromoprop-1-en-1-yl)-2-chlorobenzene (1.66 g, 7.2 mmol) was added dropwise via syringe, turning the solution dark yellow. The mixture was heated at reflux and stirred overnight. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). At the end of the reaction the solvent was removed in vacuo. The reaction residue was taken up in saturated NaHCO3 solution (70 mL) and extracted with ether (3×50 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4, gravity filtered and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 1:9, to provide 1.35 g of the title compound as a light yellow solid in a 78% yield. To an oven-dried, 100 mL, three-necked round-bottomed flask equipped with a stir bar The flask was evaporated refilled with nitrogen three times MeCN (60 mL) was added The mixture was heated at reflux The consumption of the starting material At the end of the reaction the solvent was removed in vacuo extracted with ether (3×50 mL) The combined organic layers were washed with brine (70 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 1:9

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

Procedure: To an oven-dried, 100 mL, three-necked round-bottomed flask equipped with a stir bar, two septa and a nitrogen gas inlet adaptor, was added 4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (1.0 g, 4.8 mmol) and K2CO3 (2.69 g, 19.2 mmol). The flask was evaporated and refilled with nitrogen three times, then MeCN (60 mL) was added. (E)-1-(3-bromoprop-1-en-1-yl)-2-chlorobenzene (1.66 g, 7.2 mmol) was added dropwise via syringe, turning the solution dark yellow. The mixture was heated at reflux and stirred overnight. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). At the end of the reaction the solvent was removed in vacuo. The reaction residue was taken up in saturated NaHCO3 solution (70 mL) and extracted with ether (3×50 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4, gravity filtered and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 1:9, to provide 1.35 g of the title compound as a light yellow solid in a 78% yield. To an oven-dried, 100 mL, three-necked round-bottomed flask equipped with a stir bar The flask was evaporated refilled with nitrogen three times MeCN (60 mL) was added The mixture was heated at reflux The consumption of the starting material At the end of the reaction the solvent was removed in vacuo extracted with ether (3×50 mL) The combined organic layers were washed with brine (70 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 1:9

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

Procedure: To an oven-dried, 100 mL three-necked round-bottomed flask equipped with a stir bar, two septa and a nitrogen inlet adaptor was added 4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (S17) (1.0 g, 4.8 mmol) and potassium carbonate (2.69 g, 19.2 mmol). The flask was evacuated and refilled with nitrogen three times, then MeCN (60 mL) was added. (E)-1-(3-Bromoprop-1-en-1-yl)-2-chlorobenzene (S14) (1.66 g, 7.2 mmol) was added dropwise via syringe, turning the solution dark yellow. The mixture was heated at reflux and stirred overnight. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). The solvent was removed in vacuo, and the reaction residue was taken up in sat'd NaHCO3 solution (70 mL) and extracted with ether (3×50 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 1:9, to provide 1.35 g of the title compound as a light yellow solid in a 78% yield. To an oven-dried, 100 mL three-necked round-bottomed flask equipped with a stir bar The flask was evacuated refilled with nitrogen three times MeCN (60 mL) was added The mixture was heated at reflux The consumption of the starting material The solvent was removed in vacuo extracted with ether (3×50 mL) The combined organic layers were washed with brine (70 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 1:9

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven-dried, 100 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with diethyl 2-(prop-2-yn-1-yl)malonate S13 (1.8 g, 9.1 mmol), (E)-1-(3-bromoprop-1-en-1-yl)-2-chlorobenzene S14 (2.1 g, 11.0 mmol), and THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then NaH (0.43 g of a 60% dispersion in mineral oil, 11.0 mmol) was added in one portion. The solution was stirred at 0° C. for 2 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 0.5:9.5). The reaction was then quenched with sat'd aq ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with AcOEt (3×50 mL). The combined organic layers were dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 2.55 g of the title compound as a yellow oil in 81% yield. The consumption of the starting material The reaction was then quenched with sat'd aq ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with AcOEt (3×50 mL) The combined organic layers were dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

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

Procedure: To an oven-dried, 100 mL, three-necked round-bottomed flask equipped with a stir bar, two septa and a nitrogen gas inlet adaptor, was added 4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (1.0 g, 4.8 mmol) and K2CO3 (2.69 g, 19.2 mmol). The flask was evaporated and refilled with nitrogen three times, then MeCN (60 mL) was added. (E)-1-(3-bromoprop-1-en-1-yl)-2-chlorobenzene (1.66 g, 7.2 mmol) was added dropwise via syringe, turning the solution dark yellow. The mixture was heated at reflux and stirred overnight. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). At the end of the reaction the solvent was removed in vacuo. The reaction residue was taken up in saturated NaHCO3 solution (70 mL) and extracted with ether (3×50 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4, gravity filtered and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 1:9, to provide 1.35 g of the title compound as a light yellow solid in a 78% yield. To an oven-dried, 100 mL, three-necked round-bottomed flask equipped with a stir bar The flask was evaporated refilled with nitrogen three times MeCN (60 mL) was added The mixture was heated at reflux The consumption of the starting material At the end of the reaction the solvent was removed in vacuo extracted with ether (3×50 mL) The combined organic layers were washed with brine (70 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 1:9

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

Procedure: To an oven-dried, 100 mL three-necked round-bottomed flask equipped with a stir bar, two septa and a nitrogen inlet adaptor was added 4-methyl-N-(prop-2-yn-1-yl) benzenesulfonamide (S17) (1.0 g, 4.8 mmol) and potassium carbonate (2.69 g, 19.2 mmol). The flask was evacuated and refilled with nitrogen three times, then MeCN (60 mL) was added. (E)-1-(3-Bromoprop-1-en-1-yl)-2-chlorobenzene (S14) (1.66 g, 7.2 mmol) was added dropwise via syringe, turning the solution dark yellow. The mixture was heated at reflux and stirred overnight. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). The solvent was removed in vacuo, and the reaction residue was taken up in sat'd NaHCO3 solution (70 mL) and extracted with ether (3×50 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 1:9, to provide 1.35 g of the title compound as a light yellow solid in a 78% yield. To an oven-dried, 100 mL three-necked round-bottomed flask equipped with a stir bar The flask was evacuated refilled with nitrogen three times MeCN (60 mL) was added The mixture was heated at reflux The consumption of the starting material The solvent was removed in vacuo extracted with ether (3×50 mL) The combined organic layers were washed with brine (70 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 1:9

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven-dried, 100 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with diethyl 2-(prop-2-yn-1-yl)malonate S13 (1.8 g, 9.1 mmol), (E)-1-(3-bromoprop-1-en-1-yl)-2-chlorobenzene S14 (2.1 g, 11.0 mmol), and THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then NaH (0.43 g of a 60% dispersion in mineral oil, 11.0 mmol) was added in one portion. The solution was stirred at 0° C. for 2 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 0.5:9.5). The reaction was then quenched with sat'd aq ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with AcOEt (3×50 mL). The combined organic layers were dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 2.55 g of the title compound as a yellow oil in 81% yield. The consumption of the starting material The reaction was then quenched with sat'd aq ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with AcOEt (3×50 mL) The combined organic layers were dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven-dried, 100 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with diethyl 2-(prop-2-yn-1-yl)malonate S13 (1.8 g, 9.1 mmol), (E)-1-(3-bromoprop-1-en-1-yl)-2-chlorobenzene S14 (2.1 g, 11.0 mmol), and THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then NaH (0.43 g of a 60% dispersion in mineral oil, 11.0 mmol) was added in one portion. The solution was stirred at 0° C. for 2 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 0.5:9.5). The reaction was then quenched with sat'd aq ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with AcOEt (3×50 mL). The combined organic layers were dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 2.55 g of the title compound as a yellow oil in 81% yield. The consumption of the starting material The reaction was then quenched with sat'd aq ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with AcOEt (3×50 mL) The combined organic layers were dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

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

Procedure: To an oven-dried, 100 mL, three-necked round-bottomed flask equipped with a stir bar, two septa and a nitrogen gas inlet adaptor, was added 4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (1.0 g, 4.8 mmol) and K2CO3 (2.69 g, 19.2 mmol). The flask was evaporated and refilled with nitrogen three times, then MeCN (60 mL) was added. (E)-1-(3-bromoprop-1-en-1-yl)-2-chlorobenzene (1.66 g, 7.2 mmol) was added dropwise via syringe, turning the solution dark yellow. The mixture was heated at reflux and stirred overnight. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). At the end of the reaction the solvent was removed in vacuo. The reaction residue was taken up in saturated NaHCO3 solution (70 mL) and extracted with ether (3×50 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4, gravity filtered and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 1:9, to provide 1.35 g of the title compound as a light yellow solid in a 78% yield. To an oven-dried, 100 mL, three-necked round-bottomed flask equipped with a stir bar The flask was evaporated refilled with nitrogen three times MeCN (60 mL) was added The mixture was heated at reflux The consumption of the starting material At the end of the reaction the solvent was removed in vacuo extracted with ether (3×50 mL) The combined organic layers were washed with brine (70 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 1:9

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

Procedure: To an oven-dried, 100 mL three-necked round-bottomed flask equipped with a stir bar, two septa and a nitrogen inlet adaptor was added 4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (S17) (1.0 g, 4.8 mmol) and potassium carbonate (2.69 g, 19.2 mmol). The flask was evacuated and refilled with nitrogen three times, then MeCN (60 mL) was added. (E)-1-(3-Bromoprop-1-en-1-yl)-2-chlorobenzene (S14) (1.66 g, 7.2 mmol) was added dropwise via syringe, turning the solution dark yellow. The mixture was heated at reflux and stirred overnight. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). The solvent was removed in vacuo, and the reaction residue was taken up in sat'd NaHCO3 solution (70 mL) and extracted with ether (3×50 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 1:9, to provide 1.35 g of the title compound as a light yellow solid in a 78% yield. To an oven-dried, 100 mL three-necked round-bottomed flask equipped with a stir bar The flask was evacuated refilled with nitrogen three times MeCN (60 mL) was added The mixture was heated at reflux The consumption of the starting material The solvent was removed in vacuo extracted with ether (3×50 mL) The combined organic layers were washed with brine (70 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 1:9

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven-dried, 100 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with diethyl 2-(prop-2-yn-1-yl)malonate S13 (1.8 g, 9.1 mmol), (E)-1-(3-bromoprop-1-en-1-yl)-2-chlorobenzene S14 (2.1 g, 11.0 mmol), and THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then NaH (0.43 g of a 60% dispersion in mineral oil, 11.0 mmol) was added in one portion. The solution was stirred at 0° C. for 2 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 0.5:9.5). The reaction was then quenched with sat'd aq ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with AcOEt (3×50 mL). The combined organic layers were dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 2.55 g of the title compound as a yellow oil in 81% yield. The consumption of the starting material The reaction was then quenched with sat'd aq ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with AcOEt (3×50 mL) The combined organic layers were dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5