tert-butyl (E)-but-2-enoate

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

実験手順: A solution of t-BuOH (0.50 mol, 37.1 g, 47.8 mls) in THF (500 mls) is cooled to 5° C.; then over a 30 minute period n-BuLi (0.56 mol., 350 ml, 1.6 M) is added to the solution. The resulting mixture is stirred for 40 minutes at room temperature. Crotyl chloride (0.50 mol., 52.3 g, 47.9 mls) in THF (250 mls) is added to the reaction mixture at room temperature over a 15 minute period. The resulting mixture is heated under reflux for 50 minutes. The reaction mixture is cooled to 0° C. and ice-water (800 mls) is added. The layers are separated and the aqueous layer is extracted with Et2O (3×600 mls). The organic phases are combined, dried over Na2SO4, filtered and concentrated by rotary evaporation to give a red oil. Distillation (55° C., 22 mm) yields t-butyl crotonate: 1H NMR (300 MHz, CDCl3) δ 1.46 (s, 9H), 1.83 (dd, J is 6.9, 1.7 Hz, 3H), 5.74 (dq, J is 15.5, 1.7 Hz, 1H), 6.85 (dq, J is 15.5, 6.9 Hz, 1H). The resulting mixture is heated under reflux for 50 minutes The reaction mixture is cooled to 0° C. The layers are separated the aqueous layer is extracted with Et2O (3×600 mls) dried over Na2SO4 filtered concentrated by rotary evaporation to give a red oil Distillation (55° C., 22 mm)

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

実験手順: A solution of t-BuOH (0.50 mol, 37.1 g, 47.8 mls) in THF (500 mls) is cooled to 5° C.; then over a 30 minute period n-BuLi (0.56 mol., 350 ml, 1.6M) is added to the solution. The resulting mixture is stirred for 40 minutes at room temperature. Crotyl chloride (0.50 mol., 52.3 g, 47.9 mls) in THF (250 mls) is added to the reaction mixture at room temperature over a 15 minute period. The resulting mixture is heated under reflux for 50 minutes. The reaction mixture is cooled to 0° C. and ice-water (800 mls) is added. The layers are separated and the aqueous layer is extracted with Et2O (3×600 mls). The organic phases are combined, dried over Na2SO4, filtered and concentrated by rotary evaporation to give a red oil. Distillation (55° C., 22 mm) yields t-butyl crotonate: 1H NMR (300 MHz, CDCl3) δ 1.46 (s, 9H), 1.83 (dd, J is 6.9, 1.7 Hz, 3H), 5.74 (dq, J is 15.5, 1.7 Hz, 1H), 6.85 (dq, J is 15.5, 6.9 Hz, 1H). The resulting mixture is heated under reflux for 50 minutes The reaction mixture is cooled to 0° C. The layers are separated the aqueous layer is extracted with Et2O (3×600 mls) dried over Na2SO4 filtered concentrated by rotary evaporation to give a red oil Distillation (55° C., 22 mm)

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

実験手順: A solution of t-BuOH (0.50 mol, 37.1 g, 47.8 mls) in THF (500 mls) is cooled to 5° C.; then over a 30 minute period n-BuLi (0.56 mol., 350 ml, 1.6 M) is added to the solution. The resulting mixture is stirred for 40 minutes at room temperature. Crotyl chloride (0.50 mol., 52.3 g, 47.9 mls) in THF (250 mls) is added to the reaction mixture at room temperature over a 15 minute period. The resulting mixture is heated under reflux for 50 minutes. The reaction mixture is cooled to 0° C. and ice-water (800 mls) is added. The layers are separated and the aqueous layer is extracted with Et2O (3×600 mls). The organic phases are combined, dried over Na2SO4, filtered and concentrated by rotary evaporation to give a red oil. Distillation (55° C., 22 mm) yields t-butyl crotonate: 1H NMR (300 MHz, CDCl3) δ 1.46 (s, 9H), 1.83 (dd, J is 6.9, 1.7 Hz, 3H), 5.74 (dq, J is 15.5, 1.7 Hz, 1H), 6.85 (dq, J is 15.5, 6.9 Hz, 1H). The resulting mixture is heated under reflux for 50 minutes The reaction mixture is cooled to 0° C. The layers are separated the aqueous layer is extracted with Et2O (3×600 mls) dried over Na2SO4 filtered concentrated by rotary evaporation to give a red oil Distillation (55° C., 22 mm)

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

実験手順: A solution of t-BuOH (0.50 mol, 37.1 g, 47.8 mls) in THF (500 mls) is cooled to 5° C.; then over a 30 minute period n-BuLi (0.56 mol., 350 ml, 1.6 M) is added to the solution. The resulting mixture is stirred for 40 minutes at room temperature. Crotyl chloride (0.50 mol., 52.3 g, 47.9 mls) in THF (250 mls) is added to the reaction mixture at room temperature over a 15 minute period. The resulting mixture is heated under reflux for 50 minutes. The reaction mixture is cooled to 0° C. and ice-water (800 mls) is added. The layers are separated and the aqueous layer is extracted with Et2O (3×600 mls). The organic phases are combined, dried over Na2SO4, filtered and concentrated by rotary evaporation to give a red oil. Distillation (55° C., 22 mm) yields t-butyl crotonate: 1H NMR (300 MHz, CDCl3) δ 1.46 (s, 9H), 1.83 (dd, J is 6.9, 1.7 Hz, 3H), 5.74 (dq, J is 15.5, 1.7 Hz, 1H), 6.85 (dq, J is 15.5, 6.9 Hz, 1H). The resulting mixture is heated under reflux for 50 minutes The reaction mixture is cooled to 0° C. The layers are separated the aqueous layer is extracted with Et2O (3×600 mls) dried over Na2SO4 filtered concentrated by rotary evaporation to give a red oil Distillation (55° C., 22 mm)

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

実験手順: To the mixture of (E)-tert-butyl but-2-enoate (10.0 g, 70.4 mmol) and NBS (12.5 g, 70.4 mmol) in CCl4 (150 mL) was added benzoyl peroxide (510 mg, 2.11 mmol), and the reaction was refluxed for 12 h. The mixture was cooled to room temperature, and the solid was filtered off. The filtrate was concentrated in vacuo, and purified by column chromatography to afford (E)-tert-butyl 4-bromobut-2-enoate (I-2a). 1H-NMR (400 MHz, CDCl3) δ 7.02-6.76 (m, 1H), 6.05-5.89 (m, 1H), 4.06-3.95 (m, 2H), 1.56-1.40 (m, 9H). MS calculated for C8H14BrO2 (M+H+) 221.01. found: 221.0. the reaction was refluxed for 12 h the solid was filtered off The filtrate was concentrated in vacuo purified by column chromatography

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

実験手順: To the mixture of (E)-tert-butyl but-2-enoate (10.0 g, 70.4 mmol) and NBS (12.5 g, 70.4 mmol) in CCl4 (150 mL) was added benzoyl peroxide (510 mg, 2.11 mmol), and the reaction was refluxed for 12 h. The mixture was cooled to room temperature, and the solid was filtered off. The filtrate was concentrated in vacuo, and purified by column chromatography to afford (E)-tert-butyl 4-bromobut-2-enoate (I-2a). 1H-NMR (400 MHz, CDCl3) δ 7.02-6.76 (m, 1H), 6.05-5.89 (m, 1H), 4.06-3.95 (m, 2H), 1.56-1.40 (m, 9H). MS calculated for C8H14BrO2 (M+H+) 221.01. found: 221.0. the reaction was refluxed for 12 h the solid was filtered off The filtrate was concentrated in vacuo purified by column chromatography

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

実験手順: A solution of t-BuOH (0.50 mol, 37.1 g, 47.8 mls) in THF (500 mls) is cooled to 5° C.; then over a 30 minute period n-BuLi (0.56 mol., 350 ml, 1.6 M) is added to the solution. The resulting mixture is stirred for 40 minutes at room temperature. Crotyl chloride (0.50 mol., 52.3 g, 47.9 mls) in THF (250 mls) is added to the reaction mixture at room temperature over a 15 minute period. The resulting mixture is heated under reflux for 50 minutes. The reaction mixture is cooled to 0° C. and ice-water (800 mls) is added. The layers are separated and the aqueous layer is extracted with Et2O (3×600 mls). The organic phases are combined, dried over Na2SO4, filtered and concentrated by rotary evaporation to give a red oil. Distillation (55° C., 22 mm) yields t-butyl crotonate: 1H NMR (300 MHz, CDCl3) δ1.46 (s, 9H), 1.83 (dd, J is 6.9, 1.7 Hz, 3H), 5.74 (dq, J is 15.5, 1.7 Hz, 1H), 6.85 (dq, J is 15.5, 6.9 Hz, 1H). The resulting mixture is heated under reflux for 50 minutes The reaction mixture is cooled to 0° C. The layers are separated the aqueous layer is extracted with Et2O (3×600 mls) dried over Na2SO4 filtered concentrated by rotary evaporation to give a red oil Distillation (55° C., 22 mm)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To thioglycerol (0.835 ml), t-butyl crotonate (10 ml) and triethylamine (1 ml) were added, followed by stirring at 60° C. for 48 hours. After cooling and addition of water, the reaction mixture was extracted with ethyl acetate. The extract was washed with a 5% aqueous solution of citric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, and dried over anhydrous sodium sulfate, and the solvent was distilled off, to yield the title compound (1.82 g, yield 73%) as a colorless oily substance. After cooling the reaction mixture was extracted with ethyl acetate The extract was washed with a 5% aqueous solution of citric acid a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, and dried over anhydrous sodium sulfate the solvent was distilled off

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

実験手順: The title compound (31) was prepared from compound (10) of Example 3 using the above-described procedure. [α]D21 -54.0 (c 1.81, CHCl3); νmax (CHCl3)/cm-1 1724 s (C=O); δH (300 MHz; CDCl3) 7.36-7.20 (5H, m, Ph), 3.91 (1H, q, J=6.5, PhCHCH3), 2.68 (1H, m, NCHCH2), 2.39, 2.28 (2H, ABX system, JAB =14.3, JAX =5.7, JBX =5.5, CH2CO), 1.47 (9H, s, (CH3)3C), 1.41 (2H, m, CH3CH2), 1.34 (3H, d, J=6.5, PhCHCH3), 0.85 (3H, t, J=7.3, CH3CH2); δC (50 MHz; CDCl3) 172.19 (C=O), 146.44, (Ph:Cipso), 128.53, 126.92 (Ph:Cortho, Cmeta), 126.84 (Ph:Cpara), 80.23 (C(CH3)3), 55.01, 53.71 (CHN), 39.10 (CH2CO), 28.04 (C(CH3)3), 27.78 (CH3CH2), 24.80 (NCHCH3), 10.24 (CH3CH2); m/z (CI) 278 (MH+, 100%), 248 (5), 222 (30), 192 (12), 162 (15), 105 (20); (Found: C, 73.84; H, 10.11; N, 4.93. C17H27NO2 requires C, 73.61; H, 9.81; N, 5.05%).

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

実験手順: A mixture of methyl thioglycolate (0.8 mL, 8.9 mmol), piperidine (0.12 mL, 1.2 mmol) and 2 g (14 mmol) of t-butyl crotonate was stirred at room temperature for 12 hours, followed by distillation under reduced pressure. The reaction solution was purified by column chromatography to give 2.05 g (8.2 mmol) of the title compound in a yield of 92%. followed by distillation under reduced pressure The reaction solution was purified by column chromatography

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

実験手順: A solution of t-BuOH (0.50 mol, 37.1 g, 47.8 mls) in THF (500 mls) is cooled to 5° C.; then over a 30 minute period n-BuLi (0.56 mol., 350 ml, 1.6M) is added to the solution. The resulting mixture is stirred for 40 minutes at room temperature. Crotyl chloride (0.50 mol., 52.3 g, 47.9 mls) in THF (250 mls) is added to the reaction mixture at room temperature over a 15 minute period. The resulting mixture is heated under reflux for 50 minutes. The reaction mixture is cooled to 0° C. and ice-water (800 mls) is added. The layers are separated and the aqueous layer is extracted with Et2O (3×600 mls). The organic phases are combined, dried over Na2SO4, filtered and concentrated by rotary evaporation to give a red oil. Distillation (55° C., 22 mm) yields t-butyl crotonate: 1H NMR (300 MHz, CDCl3) δ 1.46 (s, 9H), 1.83 (dd, J is 6.9, 1.7 Hz, 3H), 5.74 (dq, J is 15.5, 1.7 Hz, 1H), 6.85 (dq, J is 15.5, 6.9 Hz, 1H). The resulting mixture is heated under reflux for 50 minutes The reaction mixture is cooled to 0° C. The layers are separated the aqueous layer is extracted with Et2O (3×600 mls) dried over Na2SO4 filtered concentrated by rotary evaporation to give a red oil Distillation (55° C., 22 mm)

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

実験手順: A solution of t-BuOH (0.50 mol, 37.1 g, 47.8 mls) in THF (500 mls) is cooled to 5° C.; then over a 30 minute period n-BuLi (0.56 mol., 350 ml, 1.6 M) is added to the solution. The resulting mixture is stirred for 40 minutes at room temperature. Crotyl chloride (0.50 mol., 52.3 g, 47.9 mls) in THF (250 mls) is added to the reaction mixture at room temperature over a 15 minute period. The resulting mixture is heated under reflux for 50 minutes. The reaction mixture is cooled to 0° C. and ice-water (800 mls) is added. The layers are separated and the aqueous layer is extracted with Et2O (3×600 mls). The organic phases are combined, dried over Na2SO4, filtered and concentrated by rotary evaporation to give a red oil. Distillation (55° C., 22 mm) yields t-butyl crotonate: 1H NMR (300 MHz, CDCl3) δ 1.46 (s, 9H), 1.83 (dd, J is 6.9, 1.7 Hz, 3H), 5.74 (dq, J is 15.5, 1.7 Hz, 1H), 6.85 (dq, J is 15.5, 6.9 Hz, 1H). The resulting mixture is heated under reflux for 50 minutes The reaction mixture is cooled to 0° C. The layers are separated the aqueous layer is extracted with Et2O (3×600 mls) dried over Na2SO4 filtered concentrated by rotary evaporation to give a red oil Distillation (55° C., 22 mm)