(2-bromophenyl)methanethiol

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

実験手順: In 800 ml of tetrahydrofuran, 81.0 g (0.40 mole) of 2-bromobenzylthiol were dissolved, followed by the dropwise addition of 516 ml (0.84 mole) of n-butyl lithium (1.6 mole, a hexane solution) at −78° C. over 6 hours. After stirring at the same temperature for 1.5 hours, a solution of 79.5 g (0.40 mole) of N-tert-butoxycarbonyl-4-piperidone in 800 ml of tetrahydrofuran was added dropwise to the reaction mixture over 3 hours and then the mixture was stirred for a further 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to afford a residue. To the residue, 2 liters of 4N sulfuric acid were added and the mixture was heated under reflux for 14 hours. Under ice-cooling, the reaction mixture was made alkaline with 350 g (8.75 mole) of sodium hydroxide, followed by addition of 102 g (0.47 mole) of di-tert-butyl dicarbonate. The resulting mixture was stirred for 1 hour. The reaction mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3), whereby 56 g of the title compound were obtained as white crystals. the mixture was stirred for a further 1 hour the mixture was extracted with ethyl acetate The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure to afford a residue the mixture was heated under reflux for 14 hours Under ice-cooling The resulting mixture was stirred for 1 hour The reaction mixture was extracted with methylene chloride The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3)

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

実験手順: In 800 ml of tetrahydrofuran, 81.0 g (0.40 mole) of 2-bromobenzylthiol were dissolved, followed by the dropwise addition of 516 ml (0.84 mole) of n-butyl lithium (1.6 mole, a hexane solution) at −78° C. over 6 hours. After stirring at the same temperature for 1.5 hours, a solution of 79.5 g (0.40 mole) of N-tert-butoxycarbonyl-4-piperidone in 800 ml of tetrahydrofuran was added dropwise to the reaction mixture over 3 hours and then the mixture was stirred for a further 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to afford a residue. To the residue, 2 liters of 4N sulfuric acid were added and the mixture was heated under reflux for 14 hours. Under ice-cooling, the reaction mixture was made alkaline with 350 g (8.75 mole) of sodium hydroxide, followed by addition of 102 g (0.47 mole) of di-tert-butyl dicarbonate. The resulting mixture was stirred for 1 hour. The reaction mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3), whereby 56 g of the title compound were obtained as white crystals. the mixture was stirred for a further 1 hour the mixture was extracted with ethyl acetate The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure to afford a residue the mixture was heated under reflux for 14 hours Under ice-cooling The resulting mixture was stirred for 1 hour The reaction mixture was extracted with methylene chloride The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3)

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

実験手順: In 800 ml of tetrahydrofuran, 81.0 g (0.40 mole) of 2-bromobenzylthiol were dissolved, followed by the dropwise addition of 516 ml (0.84 mole) of n-butyl lithium (1.6 mole, a hexane solution) at −78° C. over 6 hours. After stirring at the same temperature for 1.5 hours, a solution of 79.5 g (0.40 mole) of N-tert-butoxycarbonyl-4-piperidone in 800 ml of tetrahydrofuran was added dropwise to the reaction mixture over 3 hours and then the mixture was stirred for a further 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to afford a residue. To the residue, 2 liters of 4N sulfuric acid were added and the mixture was heated under reflux for 14 hours. Under ice-cooling, the reaction mixture was made alkaline with 350 g (8.75 mole) of sodium hydroxide, followed by addition of 102 g (0.47 mole) of di-tert-butyl dicarbonate. The resulting mixture was stirred for 1 hour. The reaction mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3), whereby 56 g of the title compound were obtained as white crystals. the mixture was stirred for a further 1 hour the mixture was extracted with ethyl acetate The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure to afford a residue the mixture was heated under reflux for 14 hours Under ice-cooling The resulting mixture was stirred for 1 hour The reaction mixture was extracted with methylene chloride The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3)

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

実験手順: 81.0 g (0.40 mole) of 2-bromobenzylthiol were dissolved in 800 ml of tetrahydrofuran, and 516 ml of a solution containing 0.84 mole of butyllithium (as a 1.6 M solution in hexane) were added dropwise thereto over a period of 6 hours at a temperature of −78° C. The mixture was then stirred for 1.5 hours at the same temperature, after which 800 ml of a tetrahydrofuran solution containing 79.5 g (0.40 mole) of 1-t-butoxycarbonyl-4-piperidone was added dropwise thereto over a period of 3 hours. The solution was then stirred for a further 1 hour, and then a saturated aqueous solution of ammonium chloride was added, and the mixture was extracted with ethyl acetate. The organic extract was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure. 2 liters of 4 N aqueous sulfuric acid were added to the residue, and then the mixture was heated under reflux for 14 hours. At the end of this time, the solution was made basic by the addition of 350 g (8.75 mole) of sodium hydroxide, whilst ice-cooling, and then 102 g (0.47 mole) of di-t-butyl dicarbonate were added thereto. The mixture was then stirred for 1 hour. At the end of this time, the product was extracted with methylene chloride, and the organic extract was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography, using a 97:3 by volume mixture of hexane and ethyl acetate as the eluent, to give 56 g of the title compound as white crystals, melting at 131.0-132.5° C. (after crystallisation from hexane/ethyl acetate). were added dropwise was added dropwise over a period of 3 hours The solution was then stirred for a further 1 hour the mixture was extracted with ethyl acetate The organic extract was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The solvent was then removed by distillation under reduced pressure 2 liters of 4 N aqueous sulfuric acid were added to the residue the mixture was heated under reflux for 14 hours cooling The mixture was then stirred for 1 hour At the end of this time, the product was extracted with methylene chloride the organic extract was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The solvent was removed by distillation under reduced pressure the resulting residue was purified by silica gel column chromatography by volume mixture of hexane and ethyl acetate as the eluent to give 56 g of the title compound as white crystals, melting at 131.0-132.5° C. (after crystallisation from hexane/ethyl acetate)

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

実験手順: 81.0 g (0.40 mole) of 2-bromobenzylthiol were dissolved in 800 ml of tetrahydrofuran, and 516 ml of a solution containing 0.84 mole of butyllithium (as a 1.6 M solution in hexane) were added dropwise thereto over a period of 6 hours at a temperature of -78° C. The mixture was then stirred for 1.5 hours at the same temperature, after which 800 ml of a tetrahydrofuran solution containing 79.5 g (0.40 mole) of 1-t-butoxycarbonyl-4-piperidone was added dropwise thereto over a period of 3 hours. The solution was then stirred for a further 1 hour, and then a saturated aqueous solution of ammonium chloride was added, and the mixture was extracted with ethyl acetate. The organic extract was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure. 2 liters of 4 N aqueous sulfuric acid were added to the residue, and then the mixture was heated under reflux for 14 hours. At the end of this time, the solution was made basic by the addition of 350 g (8.75 mole) of sodium hydroxide, whilst ice-cooling, and then 102 g (0.47 mole) of di-t-butyl dicarbonate were added thereto. The mixture was then stirred for 1 hour. At the end of this time, the product was extracted with methylene chloride, and the organic extract was washed with a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography, using a 97:3 by volume mixture of hexane and ethyl acetate as the eluent, to give 56g of the title compound as white crystals, melting at 131.0-132.5° C. (after crystallisation from hexane/ethyl acetate). were added dropwise was added dropwise over a period of 3 hours The solution was then stirred for a further 1 hour the mixture was extracted with ethyl acetate The organic extract was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The solvent was then removed by distillation under reduced pressure 2 liters of 4 N aqueous sulfuric acid were added to the residue the mixture was heated under reflux for 14 hours cooling The mixture was then stirred for 1 hour At the end of this time, the product was extracted with methylene chloride the organic extract was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The solvent was removed by distillation under reduced pressure the resulting residue was purified by silica gel column chromatography by volume mixture of hexane and ethyl acetate as the eluent to give 56g of the title compound as white crystals, melting at 131.0-132.5° C. (after crystallisation from hexane/ethyl acetate)

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

実験手順: In 800 ml of tetrahydrofuran, 81.0 g (0.40 mole) of 2-bromobenzylthiol were dissolved, followed by the dropwise addition of 516 ml (0.84 mole) of n-butyl lithium (1.6 mole, a hexane solution) at −78° C. over 6 hours. After stirring at the same temperature for 1.5 hours, a solution of 79.5 g (0.40 mole) of N-tert-butoxycarbonyl-4-piperidone in 800 ml of tetrahydrofuran was added dropwise to the reaction mixture over 3 hours and then the mixture was stirred for a further 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to afford a residue. To the residue, 2 liters of 4N sulfuric acid were added and the mixture was heated under reflux for 14 hours. Under ice-cooling, the reaction mixture was made alkaline with 350 g (8.75 mole) of sodium hydroxide, followed by addition of 102 g (0.47 mole) of di-tert-butyl dicarbonate. The resulting mixture was stirred for 1 hour. The reaction mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3), whereby 56 g of the title compound were obtained as white crystals. the mixture was stirred for a further 1 hour the mixture was extracted with ethyl acetate The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure to afford a residue the mixture was heated under reflux for 14 hours Under ice-cooling The resulting mixture was stirred for 1 hour The reaction mixture was extracted with methylene chloride The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3)