5-hydroxy-4,4-dimethylpentanenitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 16.13 g (0.127 mmol) of 4,4-dimethyl-5-hydroxyvaleronitrile in 250 mL of dry CH2Cl2 was added, at 20° C., in 2 min., 24.2 mL (0.139 mmol; 1.09 eq) of diisopropylethylamine, followed after 5 min. by 25.0 g (0.165 mmol; 1.3 eq) of solid t-butyldimethylsilyl chloride, all at once. Then, 1.55 g (0.0127 mmol; 0.1 eq) of 4-dimethylaminopyridine was added and the whole was stirred at 20° C. during 18h. After removing the solvent under vacuum (aspirator) the brown residue was taken up in H2O, followed by ethyl ether. The layers were separated and the aqueous one extracted three times with 200 mL of ether. The combined organic layers were back extracted with water (100 mL), HCl 1.2N (100 mL), 5% KHCO3 (2×100 mL), dried over Na2SO4 and concentrated under vacuum to give a faint yellow oil. Distillation at 94°-97° C. (0.7 mm) gave 21 g (69%) of the title compound. TLC:(Silica),Rf 0.59(CH2Cl2), detection with molybdophosphoric acid blue on yellow. After removing the solvent under vacuum (aspirator) the brown residue The layers were separated the aqueous one extracted three times with 200 mL of ether The combined organic layers were back extracted with water (100 mL), HCl 1.2N (100 mL), 5% KHCO3 (2×100 mL) dried over Na2SO4 concentrated under vacuum to give a faint yellow oil Distillation at 94°-97° C. (0.7 mm)

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

実験手順: To a solution of 47 g (0.376 mmol) of 4,4-dimethyl-5-oxovaleronitrile in 350 mL of methanol, cooled to 0° C. (ice bath), was added, with vigorous stirring and over 15-20 min., 7.9 g (0.209 mmol; 2.22 hydride equiv.) of NaBH4. After the addition was completed, the solution was stirred an additional 30 min. at 0° C. before removing the solvent in vacuo (aspirator). To the residue was added CH2Cl2 followed by careful addition of H2O, and finally 1.2N HCl until pH=1-2 was obtained. The layers were separated and the aqueous one extracted twice (CH2Cl2), saturated with NaCl and extracted again three times with CH2Cl2. After drying the combined organic layers over Na2SO4 and removing the solvent under vacuum (aspirator) 47.7 g (95%) of the title compound, sufficiently pure for the next step, was obtained as a faint yellow oil. TLC: (Silica) Rf =0.26 (ethyl acetate dichloromethane 1:9), detection with molybdophosphoric acid (yellow spot on blue-green). was added After the addition the solution was stirred an additional 30 min. at 0° C. before removing the solvent in vacuo (aspirator) To the residue was added CH2Cl2 followed by careful addition of H2O, and finally 1.2N HCl until pH=1-2 was obtained The layers were separated the aqueous one extracted twice (CH2Cl2) saturated with NaCl and extracted again three times with CH2Cl2 After drying the combined organic layers over Na2SO4 removing the solvent under vacuum (aspirator) 47.7 g (95%) of the title compound sufficiently pure for the next step, was obtained as a faint yellow oil

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 16.13 g (0.127 mmol) of 4,4-dimethyl-5-hydroxyvaleronitrile in 250 mL of dry CH2Cl2 was added, at 20° C., in 2 min., 24.2 mL (0.139 mmol; 1.09 eq) of diisopropylethylamine, followed after 5 min. by 25.0 g (0.165 mmol; 1.3 eq) of solid t-butyldimethylsilyl chloride, all at once. Then, 1.55 g (0.0127 mmol; 0.1 eq) of 4-dimethylaminopyridine was added and the whole was stirred at 20° C. during 18h. After removing the solvent under vacuum (aspirator) the brown residue was taken up in H2O, followed by ethyl ether. The layers were separated and the aqueous one extracted three times with 200 mL of ether. The combined organic layers were back extracted with water (100 mL), HCl 1.2N (100 mL), 5% KHCO3 (2×100 mL), dried over Na2SO4 and concentrated under vacuum to give a faint yellow oil. Distillation at 94°-97° C. (0.7 mm) gave 21 g (69%) of the title compound. TLC:(Silica),Rf 0.59(CH2Cl2), detection with molybdophosphoric acid blue on yellow. After removing the solvent under vacuum (aspirator) the brown residue The layers were separated the aqueous one extracted three times with 200 mL of ether The combined organic layers were back extracted with water (100 mL), HCl 1.2N (100 mL), 5% KHCO3 (2×100 mL) dried over Na2SO4 concentrated under vacuum to give a faint yellow oil Distillation at 94°-97° C. (0.7 mm)

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

実験手順: To a solution of 47 g (0.376 mmol) of 4,4-dimethyl-5-oxovaleronitrile in 350 mL of methanol, cooled to 0° C. (ice bath), was added, with vigorous stirring and over 15-20 min., 7.9 g (0.209 mmol; 2.22 hydride equiv.) of NaBH4. After the addition was completed, the solution was stirred an additional 30 min. at 0° C. before removing the solvent in vacuo (aspirator). To the residue was added CH2Cl2 followed by careful addition of H2O, and finally 1.2N HCl until pH=1-2 was obtained. The layers were separated and the aqueous one extracted twice (CH2Cl2), saturated with NaCl and extracted again three times with CH2Cl2. After drying the combined organic layers over Na2SO4 and removing the solvent under vacuum (aspirator) 47.7 g (95%) of the title compound, sufficiently pure for the next step, was obtained as a faint yellow oil. TLC: (Silica) Rf =0.26 (ethyl acetate dichloromethane 1:9), detection with molybdophosphoric acid (yellow spot on blue-green). was added After the addition the solution was stirred an additional 30 min. at 0° C. before removing the solvent in vacuo (aspirator) To the residue was added CH2Cl2 followed by careful addition of H2O, and finally 1.2N HCl until pH=1-2 was obtained The layers were separated the aqueous one extracted twice (CH2Cl2) saturated with NaCl and extracted again three times with CH2Cl2 After drying the combined organic layers over Na2SO4 removing the solvent under vacuum (aspirator) 47.7 g (95%) of the title compound sufficiently pure for the next step, was obtained as a faint yellow oil

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 16.13 g (0.127 mmol) of 4,4-dimethyl-5-hydroxyvaleronitrile in 250 mL of dry CH2Cl2 was added, at 20° C., in 2 min., 24.2 mL (0.139 mmol; 1.09 eq) of diisopropylethylamine, followed after 5 min. by 25.0 g (0.165 mmol; 1.3 eq) of solid t-butyldimethylsilyl chloride, all at once. Then, 1.55 g (0.0127 mmol; 0.1 eq) of 4-dimethylaminopyridine was added and the whole was stirred at 20° C. during 18h. After removing the solvent under vacuum (aspirator) the brown residue was taken up in H2O, followed by ethyl ether. The layers were separated and the aqueous one extracted three times with 200 mL of ether. The combined organic layers were back extracted with water (100 mL), HCl 1.2N (100 mL), 5% KHCO3 (2×100 mL), dried over Na2SO4 and concentrated under vacuum to give a faint yellow oil. Distillation at 94°-97° C. (0.7 mm) gave 21 g (69%) of the title compound. TLC: (Silica), Rf 0.59 (CH2Cl2), detection with molybdophosphoric acid blue on yellow. After removing the solvent under vacuum (aspirator) the brown residue The layers were separated the aqueous one extracted three times with 200 mL of ether The combined organic layers were back extracted with water (100 mL), HCl 1.2N (100 mL), 5% KHCO3 (2×100 mL) dried over Na2SO4 concentrated under vacuum to give a faint yellow oil Distillation at 94°-97° C. (0.7 mm)

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

実験手順: To a solution of 47 g (0.376 mmol) of 4,4-dimethyl-5-oxovaleronitrile in 350 mL of methanol, cooled to 0° C. (ice bath), was added, with vigorous stirring and over 15-20 min., 7.9 g (0.209 mmol; 2.22 hydride equiv.) of NaBH4. After the addition was completed, the solution was stirred an additional 30 min. at 0° C. before removing the solvent in vacuo (aspirator . To the residue was added CH2Cl2 followed by careful addition of H2O, and finally 1.2N HCl until pH=1-2 was obtained. The layers were separated and the aqueous one extracted twice (CH2Cl2), saturated with NaCl and extracted again three times with CH2Cl2. After drying the combined organic layers over Na2SO4 and removing the solvent under vacuum (aspirator) 47.7 g (95%) of the title compound, sufficiently pure for the next step, was obtained as a faint yellow oil. TLC: (Silica) Rf =0.26 (ethyl acetate dichloromethane 1:9), detection with molybdophosphoric acid (yellow spot on blue-green). was added After the addition the solution was stirred an additional 30 min. at 0° C. before removing the solvent in vacuo (aspirator To the residue was added CH2Cl2 followed by careful addition of H2O, and finally 1.2N HCl until pH=1-2 was obtained The layers were separated the aqueous one extracted twice (CH2Cl2) saturated with NaCl and extracted again three times with CH2Cl2 After drying the combined organic layers over Na2SO4 removing the solvent under vacuum (aspirator) 47.7 g (95%) of the title compound sufficiently pure for the next step, was obtained as a faint yellow oil

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 16.13 g (0.127 mmol) of 4,4-dimethyl-5-hydroxyvaleronitrile in 250 mL of dry CH2Cl2 was added, at 20° C., in 2 min., 24.2 mL (0.139 mmol; 1.09 eq) of diisopropylethylamine, followed after 5 min. by 25.0 g (0.165 mmol; 1.3 eq) of solid t-butyldimethylsilyl chloride, all at once. Then, 1.55 g (0.0127 mmol; 0.1 eq) of 4-dimethylaminopyridine was added and the whole was stirred at 20° C. during 18h. After removing the solvent under vacuum (aspirator) the brown residue was taken up in H2O, followed by ethyl ether. The layers were separated and the aqueous one extracted three times with 200 mL of ether. The combined organic layers were back extracted with water (100 mL), HCl 1.2N (100 mL), 5% KHCO3 (2×100 mL), dried over Na2SO4 and concentrated under vacuum to give a faint yellow oil. Distillation at 94°-97° C. (0.7 mm) gave 21 g (69%) of the title compound. TLC:(Silica),Rf 0.59(CH2Cl2), detection with molybdophosphoric acid blue on yellow. After removing the solvent under vacuum (aspirator) the brown residue The layers were separated the aqueous one extracted three times with 200 mL of ether The combined organic layers were back extracted with water (100 mL), HCl 1.2N (100 mL), 5% KHCO3 (2×100 mL) dried over Na2SO4 concentrated under vacuum to give a faint yellow oil Distillation at 94°-97° C. (0.7 mm)

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

実験手順: To a solution of 47 g (0.376 mmol) of 4,4-dimethyl-5-oxovaleronitrile in 350 mL of methanol, cooled to 0° C. (ice bath), was added, with vigorous stirring and over 15-20 min., 7.9 g (0.209 mmol; 2.22 hydride equiv.) of NaBH4. After the addition was completed, the solution was stirred an additional 30 min. at 0° C. before removing the solvent in vacuo (aspirator). To the residue was added CH2Cl2 followed by careful addition of H2O, and finally 1.2N HCl until pH=1-2 was obtained. The layers were separated and the aqueous one extracted twice (CH2Cl2), saturated with NaCl and extracted again three times with CH2Cl2. After drying the combined organic layers over Na2SO4 and removing the solvent under vacuum (aspirator) 47.7 g (95%) of the title compound, sufficiently pure for the next step, was obtained as a faint yellow oil. TLC: (Silica) Rf =0.26 (ethyl acetate dichloromethane 1:9), detection with molybdophosphoric acid (yellow spot on blue-green). was added After the addition the solution was stirred an additional 30 min. at 0° C. before removing the solvent in vacuo (aspirator) To the residue was added CH2Cl2 followed by careful addition of H2O, and finally 1.2N HCl until pH=1-2 was obtained The layers were separated the aqueous one extracted twice (CH2Cl2) saturated with NaCl and extracted again three times with CH2Cl2 After drying the combined organic layers over Na2SO4 removing the solvent under vacuum (aspirator) 47.7 g (95%) of the title compound sufficiently pure for the next step, was obtained as a faint yellow oil