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Chemical Structure| 76093-72-6 Chemical Structure| 76093-72-6

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Chemical Structure| 76093-72-6

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Product Details of [ 76093-72-6 ]

CAS No. :76093-72-6
Formula : C14H21NO3
M.W : 251.32
SMILES Code : CC(C)(C)C(NC1=CC=CC(OC)=C1CCO)=O
MDL No. :MFCD21090869

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* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 76093-72-6 ]

[ 76093-72-6 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 75-21-8 ]
  • [ 56619-93-3 ]
  • [ 76093-72-6 ]
YieldReaction ConditionsOperation in experiment
77.1% Synthesis of N-[2-(2-hydroxyethyl)-3-methoxyphenyl]pivalamide (1b) Under the argon atmosphere, n-butyllithium (nBuLi) (2.6 M in THF, 111 mL, 289 mmol, commercial product) was slowly dropped at 0C into a tetrahydrofuran (THF) (400 mL, dehydrated, commercial product) solution of the compound 1a (30.0 g, 145 mmol). After the mixture was stirred at 0C for 2 hours, ethylene oxide (1.3 M ether solution, 175 mL, 228 mmol, commercial product) was slowly added to the mixture and stirred at 0C for 1 hour. The temperature was raised to room temperature, and then the mixture was further stirred for 2 hours. The mixture was concentrated under reduced pressure, to which a saturated ammonium chloride aqueous solution (sat. NH4Cl aq.) was added. Subsequently, the mixture was extracted with ethyl acetate (EtOAc) (100 mL * 4). The combined organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was recrystallized with ethyl acetate (EtOAc), and thus N-[2-(2-hydroxyethyl)-3-methoxyphenyl]pivalamide (compound 1b) (28.1 g, 112 mmol, 77.1%) was obtained as a colorless solid. TLC Rf= 0.40 (n-hexane/EtOAc = 3/1)
77.1% Synthesis of N-[2-(2-hydroxyethyl)-3-methoxyphenyl]pivalamide (1b) Under the argon atmosphere, n-butyllithium (nBuLi) (2.6 M in THF, 111 mL, 289 mmol, commercial product) was slowly dropped at 0 C. into a tetrahydrofuran (THF) (400 mL, dehydrated, commercial product) solution of the compound 1a (30.0 g, 145 mmol). After the mixture was stirred at 0 C. for 2 hours, ethylene oxide (1.3 M ether solution, 175 mL, 228 mmol, commercial product) was slowly added to the mixture and stirred at 0 C. for 1 hour. The temperature was raised to room temperature, and then the mixture was further stirred for 2 hours. The mixture was concentrated under reduced pressure, to which a saturated ammonium chloride aqueous solution (sat. NH4Cl aq.) was added. Subsequently, the mixture was extracted with ethyl acetate (EtOAc) (100 mL*4). The combined organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was recrystallized with ethyl acetate (EtOAc), and thus N-[2-(2-hydroxyethyl)-3-methoxyphenyl]pivalamide (compound 1b) (28.1 g, 112 mmol, 77.1%) was obtained as a colorless solid. TLC Rf=0.40 (n-hexane/EtOAc=3/1)
53% Synthesis of N-(2-(2-hydroxyethyl)-3-methoxyphenylpivalamide Into a 250 mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of <strong>[56619-93-3]N-(3-methoxyphenyl)pivalamide</strong> (11.8 g, 57.00 mmol, 1.00 equiv) in THF (200 mL). To the above was added n-BuLi (60 mL) dropwise with stirring while the temperature was maintained at 0 C. in a bath of H2O/ice. The resulting solution was allowed to react, with stirring, for 2 h. To the above was added oxirane (7 mL, 1.50 equiv) dropwise with stirring while the temperature was maintained at 0 C. in a bath of H2O/ice. The resulting solution was allowed to react, with stirring, for 1 h while the temperature was maintained at 0 C. in a bath of H2O/ice. The resulting solution was allowed to react for 2 h while the temperature was maintained at room temperature. The reaction mixture was then quenched by the adding H2O. The mixture was concentrated by evaporation under vacuum using a rotary evaporator. The resulting solution was extracted with EtOAc and the organic layers combined. The organic phase was washed with Na2CO3. The mixture was dried over Na2SO4 and concentrated by evaporation under vacuum using a rotary evaporator. The final product was purified by recrystallization from DCM/hexane. This resulted in 10.5 g (53%) of N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide as a white solid.
53% A solution of n-butyllithium in hexane (60 mL) was added dropwise to a solution of N-(3- methoxyphenyl)pivalamide (57.0 mmol) in tetrahydrofuran (200 mL) at 0 C and was maintained for 2 h. Oxirane (86 mmol) was added dropwise and the reaction mixture was maintained for 1 h at 0 C and for an additional 2 h at rt. The reaction mixture was concentrated and the residue was diluted with water (100 mL) and extracted with ethyl acetate (3 x 75 mL). The combined organic layers were washed with saturated aqueous sodium carbonate, dried (sodium sulfate), and concentrated. The final product was purified by recrystallization (dichloromethane/cyclohexane) to provide N-(2-(2-hydroxyethyl)-3- methoxyphenyl)pivalamide in 53% yield as a white solid.
53% Synthesis of N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide Into a 250 mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of <strong>[56619-93-3]N-(3-methoxyphenyl)pivalamide</strong> (11.8 g, 57.00 mmol, 1.00 equiv) in THE (200 mL). To the above was added n-BuLi (60 mL) dropwise with stirring while the temperature was maintained at 0 C. in a bath of H2O/ice. The resulting solution was allowed to react with stirring, for 2 h. To the above was added oxirane (7 mL, 1.50 equiv) dropwise with stirring while the temperature was maintained at 0 C. in a bath of H2O/ice. The resulting solution was allowed to react with stirring, for 1 h while the temperature was maintained at 0 C. in a bath of H2O/ice. The resulting solution was allowed to react for 2 h while the temperature was maintained at room temperature. The reaction mixture was then quenched by the adding H2O. The mixture was concentrated by evaporation under vacuum using a rotary evaporator. The resulting solution was extracted with EtOAc and the organic layers combined. The organic phase was washed with Na2CO3. The mixture was dried over Na2SO4 and concentrated by evaporation under vacuum using a rotary evaporator. The final product was purified by recrystallization from DCM/hexane. This resulted in 10.5 g (53%) of N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide as a white solid.
53% 3. Synthesis of N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide; A solution of n-butyllithium in hexane (60 mL) was added dropwise to a solution of <strong>[56619-93-3]N-(3-methoxyphenyl)pivalamide</strong> (57.0 mmol) in tetrahydrofuran (200 mL) at 0 C. and was maintained for 2 h. Oxirane (86 mmol) was added dropwise and the reaction mixture was maintained for 1 h at 0 C. and for an additional 2 h at rt. The reaction mixture was concentrated and the residue was diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined organic layers were washed with saturated aqueous sodium carbonate, dried (sodium sulfate), and concentrated. The final product was purified by recrystallization (dichloromethane/cyclohexane) to provide N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide in 53% yield as a white solid.
53% 3. Synthesis of A/-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide.A solution of r°-butyllithium in hexane (60 mL) was added dropwise to a solution of N-(3- methoxyphenyl)pivalamide (57.0 mmol) in tetrahydrofuran (200 mL) at 0 0C and was maintained for 2 h. Oxirane (86 mmol) was added dropwise and the reaction mixture was maintained for 1 h at 0 0C and for an additional 2 h at rt. The reaction mixture was concentrated and the residue was diluted with water (100 mL) and extracted with ethyl acetate (3 x 75 mL). The combined organic layers were washed with saturated aqueous sodium carbonate, dried (sodium sulfate), and concentrated. The final product was purified by recrystallization(dichloromethane/cyclohexane) to provide N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide in 53% yield as a white solid.
53% With (2-methylpropyl)lithium; In tetrahydrofuran; hexane; at 0 - 20℃; A solution of i-butyllithium in hexane (60 mL) was added dropwise to a solution of <strong>[56619-93-3]N-(3-methoxyphenyl)pivalamide</strong> (57.0 mmol) in tetrahydrofuran (200 mL) at 0 C. and was maintained for 2 h. Oxirane (86 mmol) was added dropwise and the reaction mixture was maintained for 1 h at 0 C. and for an additional 2 h at rt. The reaction mixture was concentrated and the residue was diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined organic layers were washed with saturated aqueous sodium carbonate, dried (sodium sulfate), and concentrated. The final product was purified by recrystallization (dichloromethane/cyclohexane) to provide N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide in 53% yield as a white solid.
53% 3. Synthesis of iV-(2-(2-hvdroxyethv0-3-methoxyphenyl)pivalamide.A solution of w-butyllithium in hexane (60 mL) was added dropwise to a solution of N-(3- methoxyphenyl)pivalamide (57.0 mmol) in tetrahydrofuran (200 mL) at 0 0C and was maintained for 2 h. Oxirane (86 mmol) was added dropwise and the reaction mixture was maintained for 1 h at 0 0C and for an additional 2 h at rt. The reaction mixture was concentrated and the residue was diluted with water (100 mL) and extracted with ethyl acetate (3 x 75 mL). The combined organic layers were washed with saturated aqueous sodium carbonate, dried (sodium sulfate), and concentrated. The final product was purified by recrystallization(dichloromethane/cyclohexane) to provide N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide in 53% yield as a white solid.
53% A solution of n-butyllithium in hexane (60 mL) was added dropwise to a solution of <strong>[56619-93-3]N-(3-methoxyphenyl)pivalamide</strong> (57.0 mmol) in tetrahydrofuran (200 mL) at 0 C. and was maintained for 2 h. Oxirane (86 mmol) was added dropwise and the reaction mixture was maintained for 1 h at 0 C. and for an additional 2 h at rt. The reaction mixture was concentrated and the residue was diluted with water (100 mL) and extracted with ethyl acetate (3*75 mL). The combined organic layers were washed with saturated aqueous sodium carbonate, dried (sodium sulfate), and concentrated. The final product was purified by recrystallization (dichloromethane/cyclohexane) to provide N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide in 53% yield as a white solid.

 

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