2-methylhex-4-ynoic acid

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0.257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyl-lithium (98.8 ml, 1.6M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1.2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0.257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyl-lithium (98.8 ml, 1.6M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1.2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0.257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyllithium (98.8 ml, 1.6 M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1,2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with etherpentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with etherpentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0.257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyl-lithium (98.8 ml, 1.6M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1.2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 20° C., 130 ml. of an approximately 1.3-molar butyllithium solution in hexane is added dropwise to a solution of 27.1 g. of diisopropylamine in 130 ml. of THF. At -20° to 0°, 6.6 ml. of propionic acid and 18 ml. of hexamethylphosphoric triamide are added dropwise to this mixture, and the latter is stirred for 35 minutes at room temperature, and then at 0° 11.6 g. of 1-bromo-2-butyne is added dropwise thereto. The mixture is then stirred for 2 hours at room temperature. Then, the reaction mixture is stirred into 300 ml. of 10% hydrochloric acid, extracted three times with a mixture of pentane/ether (1+1), the organic extract is washed neutral with water, dried with magnesium sulfate, and the solvent is removed by distillation. After distilling the remainder in a bulb tube at 12 torr and 114°, 7.8 g. of 2-methyl-4-hexynoic acid is obtained as a colorless liquid. At 20° C. At -20° to 0° at 0° The mixture is then stirred for 2 hours at room temperature Then, the reaction mixture is stirred into 300 ml of 10% hydrochloric acid, extracted three times with a mixture of pentane/ether (1+1) the organic extract is washed neutral with water dried with magnesium sulfate the solvent is removed by distillation After distilling the remainder in a bulb tube at 12 torr and 114°, 7.8 g

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 20° C., 130 ml. of an approximately 1.3-molar butyllithium solution in hexane is added dropwise to a solution of 27.1 g. of diisopropylamine in 130 ml. of THF. At -20° to 0°, 6.6 ml. of propionic acid and 18 ml. of hexamethylphosphoric triamide are added dropwise to this mixture, and the latter is stirred for 35 minutes at room temperature, and then at 0° 11.6 g. of 1-bromo-2-butyne is added dropwise thereto. The mixture is then stirred for 2 hours at room temperature. Then, the reaction mixture is stirred into 300 ml. of 10% hydrochloric acid, extracted three times with a mixture of pentane/ether (1+1), the organic extract is washed neutral with water, dried with magnesium sulfate, and the solvent is removed by distillation. After distilling the remainder in a bulb tube at 12 torr and 114°, 7.8 g. of 2-methyl-4-hexynoic acid is obtained as a colorless liquid. At 20° C. At -20° to 0° at 0° The mixture is then stirred for 2 hours at room temperature Then, the reaction mixture is stirred into 300 ml of 10% hydrochloric acid, extracted three times with a mixture of pentane/ether (1+1) the organic extract is washed neutral with water dried with magnesium sulfate the solvent is removed by distillation After distilling the remainder in a bulb tube at 12 torr and 114°, 7.8 g

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0.257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyllithium (98.8 ml, 1.6M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1.2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with etherpentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with etherpentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0. 257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyllithium (98.8 ml, 1.6M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1.2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with etherpentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with etherpentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0.257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyl-lithium (98.8 ml, 1.6M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1.2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0.257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyllithium (98.8 ml, 1.6 M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1,2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with etherpentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with etherpentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylamine (26.0 g, 0.257 mmol, 3.1 eq) in 130 ml of tetrahydrofuran initially at -50° C. is treated dropwise with n-butyl-lithium (98.8 ml, 1.6M, 0.158 mol, 1.9 eq) over an 8 minute period while allowing the temperature to rise to -25° C. After 5 minutes longer at -20° C., the reaction mixture is treated dropwise with a mixture of hexamethylphosphoramide (17.8 g, 0.099 mol, 1.2 eq) and propionic acid (6.14 g, 0.083 mol, 1.0 eq) over a 7 minute period while the temperature rises to 0° C. Following addition the reaction mixture is warmed to room temperature and maintained there for 35 minutes. The contents are then cooled to 0° C. in an ice bath, treated dropwise over a 12 minute period with 1-bromo-2-butyne (11.0 g, 0.083 mol, 1.0 eq) in 8 ml of tetrahydrofuran. The temperature, which rises to 16° C. during addition, is allowed to warm to room temperature thereafter where it is maintained for 2 hours. The contents are carefully poured into 300 ml of 10% HCl with stirring (exothermic) followed by 500 ml of ether-pentane (1:1). The organic layer is separated and the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume. The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate and concentrated at reduced pressure to provide 11.1 g (over theory) of 2-methyl-4-hexynoic acid which is converted to the methyl ester by treatment with methyl iodide. to rise to -25° C rises to 0° C addition the reaction mixture maintained there for 35 minutes The contents are then cooled to 0° C. in an ice bath The temperature, which rises to 16° C. during addition to warm to room temperature where it is maintained for 2 hours The organic layer is separated the aqueous phase extracted 2 more times with ether-pentane (1:1) giving 1800 ml of total extract volume The combined extracts are washed with water 2×60 ml) and the combined organic extracts are dried over anhydrous sodium sulfate, magnesium sulfate concentrated at reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 20° C., 130 ml. of an approximately 1.3-molar butyllithium solution in hexane is added dropwise to a solution of 27.1 g. of diisopropylamine in 130 ml. of THF. At -20° to 0°, 6.6 ml. of propionic acid and 18 ml. of hexamethylphosphoric triamide are added dropwise to this mixture, and the latter is stirred for 35 minutes at room temperature, and then at 0° 11.6 g. of 1-bromo-2-butyne is added dropwise thereto. The mixture is then stirred for 2 hours at room temperature. Then, the reaction mixture is stirred into 300 ml. of 10% hydrochloric acid, extracted three times with a mixture of pentane/ether (1+1), the organic extract is washed neutral with water, dried with magnesium sulfate, and the solvent is removed by distillation. After distilling the remainder in a bulb tube at 12 torr and 114°, 7.8 g. of 2-methyl-4-hexynoic acid is obtained as a colorless liquid. At 20° C. At -20° to 0° at 0° The mixture is then stirred for 2 hours at room temperature Then, the reaction mixture is stirred into 300 ml of 10% hydrochloric acid, extracted three times with a mixture of pentane/ether (1+1) the organic extract is washed neutral with water dried with magnesium sulfate the solvent is removed by distillation After distilling the remainder in a bulb tube at 12 torr and 114°, 7.8 g