ethyl (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 479.2 mL (0.958 mole) methylamine (2M in tetrahydrofuran) was added dropwise to 99.44 gm ethyl crotonate with stirring. After stirring 5 days at room temperature the reaction mixture was concentrated under reduced pressure to remove tetrahydrofuran. The residue was distilled to provide 91.25 gm (72%) of the desired product in 2 fractions. MS(FD): m/e=145 (M+); EA: Calculated for: C7H15NO2: Theory: C, 57.90; H, 10.41; N, 9.65. Found: C, 57.61; H, 10.66; N, 9.88. After stirring 5 days at room temperature the reaction mixture was concentrated under reduced pressure to remove tetrahydrofuran The residue was distilled

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

実験手順: A solution of 11.86 g (0.1 moles) of ethyl crotonate and 19.50 g (0.1 moles) of ρ-toluenesulfonylmethylisocyanide in 500 mL of a 2:1 ether/dimethylsulfoxide was added dropwise into a suspension of 6.8 g of sodium hydride (60% mineral oil dispension, 0.17 moles) in ether at room temperature. Upon completion of addition the reaction mixture was stirred for 30 min and diluted with 400 mL of water. The aqueous layer was extracted with 3×100 mL of ether. The combined ether extracts were passed through a column of alumina eluting with dichloromethane. The organic solvent was evaporated and the resulting residue was solidified on standing. The solid was washed with hexane and dried at 40° C. in vacuum oven overnight to yield 12.38 g (80%) of the title compound. Upon completion of addition the reaction mixture The aqueous layer was extracted with 3×100 mL of ether The organic solvent was evaporated The solid was washed with hexane dried at 40° C. in vacuum oven overnight

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

実験手順: A solution of 8-bromo-2-methylquinoline (2.00 g, 9.01 mmol), (E)-ethyl but-2-enoate (3.36 mL, 27.0 mmol), N-cyclohexyl-N-methylcyclohexanamine (5.79 mL, 27.0 mmol), and Pd(PtBu3)2 (0.23 g, 0.45 mmol) in dioxane (10 mL) was stirred at reflux for 20 hours. After cooling to ambient temperature, water (20 mL) and ethyl acetate (30 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 40M column, 0-100% CH3CN/water gradient; 30 column volumes) to give (Z)-ethyl 3-(2-methylquinolin-8-yl)but-2-enoate (0.81 g, 35.2%) as a solid. at reflux for 20 hours The organic layer was separated washed with brine dried (sodium sulfate) filtered concentrated under reduced pressure The residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit

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

実験手順: Ethyl 3-(4-benzylpiperidin-1-yl)butyrate. A solution of 4-benzyl piperidine (0.50 mL, 2.8 mmol) and ethyl crotonate (0.46 mL, 3.4 mol) in isopropanol (10 mL) was refluxed for 24 h and was concentrated in vacuo. The crude compound was purified by filtration on silica gel using CH2Cl2/MeOH as solvent to afford the title compound as a pale yellow oil (0.64 g, 74%): 1H NMR (CDCl3) δ 1.09 (d, J=6.6 Hz, 3H), 1.30 (t, J=6.9 Hz, 3H), 1.20-1.40 (m, 2H), 1.45-1.61 (m, 1H), 1.68 (bd, J=12.3 Hz, 2H), 2.10-2.35 (m, 3H), 2.57 (d, J6.9 Hz, 2H), 2.50-2.70 (m, 1H), 2.82 (bd, J=10.8 Hz, 2H), 3.15-3.30 (m, 1H), 4.18 (q, J=6.9 Hz, 2H), 7.18 (d, J=7.2 Hz, 2H), 7.24 (m, 1H), 7.32 (t, J=6.9 Hz, 2H). was concentrated in vacuo The crude compound was purified by filtration on silica gel

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 10-3 (500 mg, 1.4 mmoles), ethyl crotonate (1.7 mL, 3.8 mmoles), Pd(OAc)2 (31 mg, 0.14 mmoles), NEt3 (0.78 mL, 8 mmoles), tri-o-tolylphosphine (170 mg, 0.56 mmoles), and CH3CN (7 mL) was heated in a sealed tube at 100° C. for 24 hours. The cooled reaction mixture was diluted with EtOAc and then washed with H2O, 10% KHSO4, saturated NaHCO3, and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 25% EtOAc/hexanes) gave 12-1 as a waxy yellow solid. Rf 0.33 (silica, 25% EtOAc/hexanes). The cooled reaction mixture washed with H2O, 10% KHSO4, saturated NaHCO3, and brine dried (MgSO4) concentrated

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 10-3 (500 mg, 1.4 mmoles), ethyl crotonate (1.7 mL, 3.8 mmoles), Pd(OAc)2 (31 mg, 0.14 mmoles), NEt3 (0.78 mL, 8 mmoles), tri-o-tolylphosphine (170 mg, 0.56 mmoles), and CH3CN (7 mL) was heated in a sealed tube at 100° C. for 24 hours. The cooled reaction mixture was diluted with EtOAc and then washed with H2O, 10% KHSO4, saturated NaHCO3, and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 25% EtOAc/hexanes) gave 12-1 as a waxy yellow solid. Rf 0.33 (silica, 25% EtOAc/hexanes). The cooled reaction mixture washed with H2O, 10% KHSO4, saturated NaHCO3, and brine dried (MgSO4) concentrated

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

実験手順: Same as Example 1, but with the use of 1.1 mole of sodium ethylate in the form of a solution of 14.5% by weight in ethanol with a content of 0.62 wt.-% of NaOH, and 200 ml of ethanol containing 0.28 wt.-% of H2O, one mole of allyl chloride is reacted at 1.5 at. and a pH of 10.0. The filtration and distillation yield 94.0 g of crotonic acid ethyl ester (yield 89.5%, 6.9 g of vinyl acetic acid ethyl ester (yield 6.6%) and 0.7 g of β-ethoxybutyric acid ethyl ester (yield 0.5%) for a transformation of 92.4% of the allyl chloride.

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

実験手順: Same as Example 1, but with the use of 1.1 mole of sodium ethylate in the form of a solution of 14.5% by weight in ethanol with a content of 0.62 wt.-% of NaOH, and 200 ml of ethanol containing 0.28 wt.-% of H2O, one mole of allyl chloride is reacted at 1.5 at. and a pH of 10.0. The filtration and distillation yield 94.0 g of crotonic acid ethyl ester (yield 89.5%, 6.9 g of vinyl acetic acid ethyl ester (yield 6.6%) and 0.7 g of β-ethoxybutyric acid ethyl ester (yield 0.5%) for a transformation of 92.4% of the allyl chloride.

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

実験手順: Coupling of 3 bromobenzaldehyde with ethyl crotonate following the method used in Example 26 gave ethyl 3-(3-formylphenyl)but-2-enoate as a light yellow oil Yield (0.547, 23%): 1H NMR (300 MHz, CDCl3) δ 10.05 (s, 1H), 7.99 (t, J=1.6 Hz, 1H), 7.87 (dt, J=7.6, 1.3 Hz, 1H), 7.74 (m, 1H), 7.56 (t, J=7.6 Hz, 1H), 6.19 (q, J=1.2 Hz, 1H), 4.23 (q, J=7.2 Hz, 2H), 2.61 (d, J=1.2 Hz, 3H), 1.33 (t, J=7.2 Hz, 3H).

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

実験手順: Coupling of 3 bromobenzaldehyde with ethyl crotonate following the method used in Example 26 gave ethyl 3-(3-formylphenyl)but-2-enoate as a light yellow oil Yield (0.547, 23%): 1H NMR (300 MHz, CDCl3) δ 10.05 (s, 1H), 7.99 (t, J=1.6 Hz, 1H), 7.87 (dt, J=7.6, 1.3 Hz, 1H), 7.74 (m, 1H), 7.56 (t, J=7.6 Hz, 1H), 6.19 (q, J=1.2 Hz, 1H), 4.23 (q, J=7.2 Hz, 2H), 2.61 (d, J=1.2 Hz, 3H), 1.33 (t, J=7.2 Hz, 3H).

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

実験手順: Based on D. O. Cheng, T. L. Bowman, E. LeGoff, J. Heterocyclic Chem. 13, 1145 (1976), 3,4-dimethylpyrrole was synthesized starting from p-toluol-sulfonylmethyliso-cyanide and crotonic-acid-ethyl-ester. The dimethyl compound was quickly obtained after reduction of the intermediary 3-(ethoxycarbonyl)-4-methylpyrrole, but at only 18% total yield. The material had a melting point of 25°-28° C. H-NMR (CDCl3): 2.04 (s, 6H), 6.50 (d, 2H), 7.33 (s br, 1H).

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

実験手順: To a solution containing 10.0 g 3,4 dimethoxy-6-chlorobenzaldehyde and 8 ml of ethyl crotonate in 60 ml of N-methylpyrrolidone 6.0 g of potassium tert.-butoxide was added while stirring . The solution was stirred for 0.5 h more at 20° C. and poured then to a mixture of ice and hydrochloric acid. The solution was extracted with ether. The ether solution was washed with water and extracted with 2.5 N NaOH-solution. The aqueous phase was acidified with hydrochloric acid and the semisolid product was separated. Yield 10.8 g (81%). was added The solution was stirred for 0.5 h more at 20° C. poured The solution was extracted with ether The ether solution was washed with water extracted with 2.5 N NaOH-solution the semisolid product was separated