89% |
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1) 4-Ethoxycarbonyl-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole To a mixture of 1.53M solution of butyllithium in hexane (36 ml, 54.7 mmol) and tetrahydrofuran (240 ml) was added a solution of alpha-(p-toluenesulfonyl)-4-fluorobenzylisocyanide (15.90 g, 54.7 mmol) in tetrahydrofuran (120 ml) at -45C under stirring, and the resulting mixture was stirred at the same temperature for 10 minutes. Furthermore, to the reaction mixture was added 95% lithium bromide (25.00 g, 273 mmol) at the same temperature under stirring, and the resulting mixture was stirred at the same temperature for 30 minutes. After stirring, a solution of ethyl 3-(4-pyridyl)acrylate (8.73 g, 49.2 mmol) in tetrahydrofuran (120 ml) was added to the reaction mixture at the same temperature under stirring, and the resulting mixture was stirred at the same temperature for one hour. Subsequently, the reaction vessel was removed from the cooling bath, and the reaction mixture was stirred at room temperature for one hour. After stirring, water (500 ml) was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The separated organic layer containing the desired compound was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The solid thus obtained was washed with diethyl ether to afford the title compound (13.61 g) in a yield of 89% as a pale yellow powder. 1H-NMR (500MHz, DMSO-d6) deltappm: 8.84 (1H, br.s), 8.51 (2H, d, J=7Hz), 7.58 (1H, d, J=3Hz), 7.21 (2H, d, J=6Hz), 7.11 (2H, dd, J=9Hz, 5Hz), 6.97 (2H, t, J=9Hz), 4.18 (2H, q, J=7Hz), 1.20 (3H, t, J=7Hz). |
89% |
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36 ml (54.7 mmol) of a 1.53 N solution of butyllithium in hexane were added to 240 ml of tetrahydrofuran. A solution of 15.90 g (54.7 mmol) of alpha -(p-toluene-sulfonyl)-4-fluorobenzylisonitrile in 120 ml of tetrahydrofuran was then added to the resulting solution at -45 DEG C, followed by stirring of the resulting mixture for 10 minutes at the same temperature. At the end of this time, 25.00 g (273 mmol) of 95% lithium bromide were added, the resulting mixture was stirred for 30 minutes and then a solution of 8.73 g (49.2 mmol) of ethyl 3-(4-pyridyl)acrylate in 120 ml of tetrahydrofuran was added. The resulting mixture was stirred at the same temperature for 1 hour and then the cooling bath was removed and the mixture was stirred at room temperature for a further 1 hour. At the end of this time, 500 ml of water were added and the resulting mixture was extracted with ethyl acetate. The organic extract was washed with water and then dried over anhydrous sodium sulfate, after which it was concentrated by evaporation under reduced pressure to afford a solid. The solid was washed with diethyl ether to give 13.61 g (yield 89%) of the title compound as a pale yellow powder. <1>H-Nuclear magnetic resonance spectrum (500 MHz, CDCl3) delta ppm: 8.84 (1H, broad singlet); 8.51 (2H, doublet, J=7 Hz); 7.58 (1H, doublet, J=3 Hz); 7.21 (2H, doublet, J=6 Hz); 7.11 (2H, doublet of doublets, J=9 Hz, 5 Hz); 6.97 (2H, triplet, J=9 Hz); 4.18 (2H, quartet, J=7 Hz); 1.20 (3H, triplet, J=7 Hz). |
89% |
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36 ml (54.7 mmol) of a 1.53 N solution of butyllithium in hexane were added to 240 ml of tetrahydrofuran.A solution of 15.90 g (54.7 mmol) of alpha-(p-toluenesulfonyl)-4-fluorobenzylisonitrile in 120 ml of tetrahydrofuran was then added to the resulting solution at -45 C., followed by stirring of the resulting mixture for 10 minutes at the same temperature.At the end of this time, 25.00 g (273 mmol) of 95% lithium bromide were added, the resulting mixture was stirred for 30 minutes and then a solution of 8.73 g (49.2 mmol) of ethyl 3-(4-pyridyl)acrylate in 120 ml of tetrahydrofuran was added.The resulting mixture was stirred at the same temperature for 1 hour and then the cooling bath was removed and the mixture was stirred at room temperature for a further 1 hour.At the end of this time, 500 ml of water were added and the resulting mixture was extracted with ethyl acetate.The organic extract was washed with water and then dried over anhydrous sodium sulfate, after which it was concentrated by evaporation under reduced pressure to afford a solid.The solid was washed with diethyl ether to give 13.61 g (yield 89%) of the title compound as a pale yellow powder. 1H-Nuclear magnetic resonance spectrum (500 MHz, CDCl3) delta ppm: 8.84 (1H, broad singlet); 8.51 (2H, doublet, J=7 Hz); 7.58 (1H, doublet, J=3 Hz); 7.21 (2H, doublet, J=6 Hz); 7.11 (2H, doublet of doublets, J=9 Hz, 5 Hz); 6.97 (2H, triplet, J=9 Hz); 4.18 (2H, quartet, J=7 Hz); 1.20 (3H, triplet, J=7 Hz). 36 ml (54.7 mmol) of a 1.53 N solution of butyllithium in hexane were added to 240 ml of tetrahydrofuran.A solution of 15.90 g (54.7 mmol) of alpha-(p-toluenesulfonyl)-4-fluorobenzylisonitrile in 120 ml of tetrahydrofuran was then added to the resulting solution at -45 C., followed by stirring of the resulting mixture for 10 minutes at the same temperature.At the end of this time, 25.00 g (273 mmol) of 95% lithium bromide were added, the resulting mixture was stirred for 30 minutes and then a solution of 8.73 g (49.2 mmol) of ethyl 3-(4-pyridyl)acrylate in 120 ml of tetrahydrofuran was added.The resulting mixture was stirred at the same temperature for 1 hour and then the cooling bath was removed and the mixture was stirred at room temperature for a further 1 hour.At the end of this time, 500 ml of water were added and the resulting mixture was extracted with ethyl acetate.The organic extract was washed with water and then dried over anhydrous sodium sulfate, after which it was concentrated by evaporation under reduced pressure to afford a solid.The solid was washed with diethyl ether to give 13.61 g (yield 89%) of the title compound as a pale yellow powder. 1H-Nuclear magnetic resonance spectrum (500 MHz, CDCl3) delta ppm: 8.84 (1H, broad singlet); 8.51 (2H, doublet, J=7 Hz); 7.58 (1H, doublet, J=3 Hz); 7.21 (2H, doublet, J=6 Hz); 7.11 (2H, doublet of doublets, J=9 Hz, 5 Hz); 6.97 (2H, triplet, J=9 Hz); 4.18 (2H, quartet, J=7 Hz); 1.20 (3H, triplet, J=7 Hz). |