ethyl 2-(1-hydroxycyclobutyl)propanoate

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

実験手順: H2SO4 (3.90 mL, 73.2 mmol) was slowly added to a mixture of ethyl 2-(1-hydroxycyclobutyl)propionate (12.5 g, 72.6 mmol) and benzonitrile (75 mL) at room temperature. The mixture was stirred for 1 hour at room temperature, then 80° C. for 1 hour. The mixture was cooled in an ice-water bath and 2N NaOH solution was added until the mixture reached pH=7. The mixture was extracted with ethyl acetate, the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (AcOEt:Hexane=5:1) of the residue gave the title compound as a pale yellow solid (9.24 g, 46%). 1H-NMR (400 MHz, CDCl3) δ 1.25 (3H, t, J=7.3 Hz), 1.30 (3H, d, J=7.3 Hz), 1.73-1.87 (1H, m), 1.98-2.09 (2H, m), 2.21-2.32 (1H, m), 2.53-2.63 (1H, m), 2.84-2.94 (1H, m), 3.11 (1H, q, J=7.3 Hz), 4.08-4.20 (2H, m), 6.88 (1H, brs), 7.40-7.52 (3H, m), 7.75-7.80 (2H, m). 80° C. for 1 hour The mixture was cooled in an ice-water bath The mixture was extracted with ethyl acetate the combined organic extracts were dried over anhydrous Na2SO4 filtered concentrated in vacuo

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

実験手順: Trimethylchlorosilane (950 μL, 7.43 mmol) was added by syringe to a suspension of zinc powder (6.65 g, 0.102 mol) in absolute Et2O (170 mL). The mixture was stirred for 15 minutes at room temperature, heated to reflux, the heat source removed, and ethyl 2-bromopropionate (10.1 mL, 77.8 mmol) was added at such a rate that the ether gently boiled. After being heated to reflux for 1 hour, the mixture was stirred for 1 hour at room temperature. A solution of cyclobutanone (5.00 g, 63.2 mmol) in Et2O (10 mL) was added while the temperature of the mixture was maintained at 19-20° C. by intermittent cooling. After stirring for 1 hour at room temperature, the mixture was poured into iced 25% ammonia (400 mL). The aqueous phase was extracted with ether, the combined organic phases were dried over K2CO3, and concentrated. the title compound was given as a colorless oil (12.9 g, 100%). 1H-NMR (400 MHz, CDCl3) δ 1.21 (3H, d, J=6.8 Hz), 1.29 (3H, t, J=7.3 Hz), 1.51-1.64 (1H, m), 1.80-1.90 (1H, m), 1.96-2.17 (4H, m), 2.70 (1H, q, J=7.3 Hz), 3.44 (1H, s), 4.18 (2H, qd, J=7.3 and 1.2 Hz). heated to reflux the heat source removed After being heated to reflux for 1 hour the mixture was stirred for 1 hour at room temperature was maintained at 19-20° C. by intermittent cooling After stirring for 1 hour at room temperature The aqueous phase was extracted with ether the combined organic phases were dried over K2CO3 concentrated

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

実験手順: Trimethylchlorosilane (950 μL, 7.43 mmol) was added by syringe to a suspension of zinc powder (6.65 g, 0.102 mol) in absolute Et2O (170 mL). The mixture was stirred for 15 minutes at room temperature, heated to reflux, the heat source removed, and ethyl 2-bromopropionate (10.1 mL, 77.8 mmol) was added at such a rate that the ether gently boiled. After being heated to reflux for 1 hour, the mixture was stirred for 1 hour at room temperature. A solution of cyclobutanone (5.00 g, 63.2 mmol) in Et2O (10 mL) was added while the temperature of the mixture was maintained at 19-20° C. by intermittent cooling. After stirring for 1 hour at room temperature, the mixture was poured into iced 25% ammonia (400 mL). The aqueous phase was extracted with ether, the combined organic phases were dried over K2CO3, and concentrated. the title compound was given as a colorless oil (12.9 g, 100%). 1H-NMR (400 MHz, CDCl3) δ 1.21 (3H, d, J=6.8 Hz), 1.29 (3H, t, J=7.3 Hz), 1.51-1.64 (1H, m), 1.80-1.90 (1H, m), 1.96-2.17 (4H, m), 2.70 (1H, q, J=7.3 Hz), 3.44 (1H, s), 4.18 (2H, qd, J=7.3 and 1.2 Hz). heated to reflux the heat source removed After being heated to reflux for 1 hour the mixture was stirred for 1 hour at room temperature was maintained at 19-20° C. by intermittent cooling After stirring for 1 hour at room temperature The aqueous phase was extracted with ether the combined organic phases were dried over K2CO3 concentrated

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

実験手順: H2SO4 (3.90 mL, 73.2 mmol) was slowly added to a mixture of ethyl 2-(1-hydroxycyclobutyl)propionate (12.5 g, 72.6 mmol) and benzonitrile (75 mL) at room temperature. The mixture was stirred for 1 hour at room temperature, then 80° C. for 1 hour. The mixture was cooled in an ice-water bath and 2N NaOH solution was added until the mixture reached pH=7. The mixture was extracted with ethyl acetate, the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (AcOEt:Hexane=5:1) of the residue gave the title compound as a pale yellow solid (9.24 g, 46%). 1H-NMR (400 MHz, CDCl3) δ 1.25 (3H, t, J=7.3 Hz), 1.30 (3H, d, J=7.3 Hz), 1.73-1.87 (1H, m), 1.98-2.09 (2H, m), 2.21-2.32 (1H, m), 2.53-2.63 (1H, m), 2.84-2.94 (1H, m), 3.11 (1H, q, J=7.3 Hz), 4.08-4.20 (2H, m), 6.88 (1H, brs), 7.40-7.52 (3H, m), 7.75-7.80 (2H, m). 80° C. for 1 hour The mixture was cooled in an ice-water bath The mixture was extracted with ethyl acetate the combined organic extracts were dried over anhydrous Na2SO4 filtered concentrated in vacuo

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

実験手順: Trimethylchlorosilane (950 μL, 7.43 mmol) was added by syringe to a suspension of zinc powder (6.65 g, 0.102 mol) in absolute Et2O (170 mL). The mixture was stirred for 15 minutes at room temperature, heated to reflux, the heat source removed, and ethyl 2-bromopropionate (10.1 mL, 77.8 mmol) was added at such a rate that the ether gently boiled. After being heated to reflux for 1 hour, the mixture was stirred for 1 hour at room temperature. A solution of cyclobutanone (5.00 g, 63.2 mmol) in Et2O (10 mL) was added while the temperature of the mixture was maintained at 19-20° C. by intermittent cooling. After stirring for 1 hour at room temperature, the mixture was poured into iced 25% ammonia (400 mL). The aqueous phase was extracted with ether, the combined organic phases were dried over K2CO3, and concentrated. the title compound was given as a colorless oil (12.9 g, 100%). 1H-NMR (400 MHz, CDCl3) δ1.21 (3H, d, J=6.8 Hz), 1.29 (3H, t, J=7.3 Hz), 1.51-1.64 (1H, m), 1.80-1.90 (1H, m), 1.96-2.17 (4H, m), 2.70 (1H, q, J=7.3 Hz), 3.44 (1H, s), 4.18 (2H, qd, J=7.3 and 1.2 Hz). heated to reflux the heat source removed After being heated to reflux for 1 hour the mixture was stirred for 1 hour at room temperature was maintained at 19-20° C. by intermittent cooling After stirring for 1 hour at room temperature The aqueous phase was extracted with ether the combined organic phases were dried over K2CO3 concentrated

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

実験手順: H2SO4 (3.90 mL, 73.2 mmol) was slowly added to a mixture of ethyl 2-(1-hydroxycyclobutyl)propionate (12.5 g, 72.6 mmol) and benzonitrile (75 mL) at room temperature. The mixture was stirred for 1 hour at room temperature, then 80° C. for 1 hour. The mixture was cooled in an ice-water bath and 2N NaOH solution was added until the mixture reached pH=7. The mixture was extracted with ethyl acetate, the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (AcOEt:Hexane=5:1) of the residue gave the title compound as a pale yellow solid (9.24 g, 46%). 1H-NMR (400 MHz, CDCl3) δ 1.25 (3H, t, J=7.3 Hz), 1.30 (3H, d, J=7.3 Hz), 1.73-1.87 (1H, m), 1.98-2.09 (2H, m), 2.21-2.32 (1H, m), 2.53-2.63 (1H, m), 2.84-2.94 (1H, m), 3.11 (1H, q, J=7.3 Hz), 4.08-4.20 (2H, m), 6.88 (1H, brs), 7.40-7.52 (3H, m), 7.75-7.80 (2H, m). 80° C. for 1 hour The mixture was cooled in an ice-water bath The mixture was extracted with ethyl acetate the combined organic extracts were dried over anhydrous Na2SO4 filtered concentrated in vacuo

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

実験手順: Trimethylchlorosilane (950 μL, 7.43 mmol) was added by syringe to a suspension of zinc powder (6.65 g, 0.102 mol) in absolute Et2O (170 mL). The mixture was stirred for 15 minutes at room temperature, heated to reflux, the heat source removed, and ethyl 2-bromopropionate (10.1 mL, 77.8 mmol) was added at such a rate that the ether gently boiled. After being heated to reflux for 1 hour, the mixture was stirred for 1 hour at room temperature. A solution of cyclobutanone (5.00 g, 63.2 mmol) in Et2O (10 mL) was added while the temperature of the mixture was maintained at 19-20° C. by intermittent cooling. After stirring for 1 hour at room temperature, the mixture was poured into iced 25% ammonia (400 mL). The aqueous phase was extracted with ether, the combined organic phases were dried over K2CO3, and concentrated. the title compound was given as a colorless oil (12.9 g, 100%). 1H-NMR (400 MHz, CDCl3) δ 1.21 (3H, d, J=6.8 Hz), 1.29 (3H, t, J=7.3 Hz), 1.51-1.64 (1H, m), 1.80-1.90 (1H, m), 1.96-2.17 (4H, m), 2.70 (1H, q, J=7.3 Hz), 3.44 (1H, s), 4.18 (2H, qd, J=7.3 and 1.2 Hz). heated to reflux the heat source removed After being heated to reflux for 1 hour the mixture was stirred for 1 hour at room temperature was maintained at 19-20° C. by intermittent cooling After stirring for 1 hour at room temperature The aqueous phase was extracted with ether the combined organic phases were dried over K2CO3 concentrated