ethyl 4,4,4-trifluoro-3-(nitromethyl)butanoate

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 100 mL round-bottomed flask, KOH (356 mg, 5.45 mmol) was combined with H2O (50 ml) to give a colorless solution and cooled to 0° C. 4,4,4-Trifluoro-3-nitromethyl-butyric acid ethyl ester (1.25 g, 5.45 mmol) in 10 ml THF was added and the resulting reaction mixture was stirred for 20 min. This was followed by addition of MgSO4 (657 mg, 5.45 mmol) in 5 ml of H2O then by KMnO4 (862 mg, 5.45 mmol) in 30 ml of H2O. The resulting reaction mixture was stirred for 30 min, filtered through celite and the celite cake washed with CH2Cl2. The combined filtrate and washes were washed with brine, dried over Na2SO4, filtered and concentrated to afford 4,4,4-trifluoro-3-formyl-butyric acid ethyl ester as a liquid which was used without purification. to give a colorless solution the resulting reaction mixture The resulting reaction mixture was stirred for 30 min filtered through celite the celite cake washed with CH2Cl2 The combined filtrate and washes were washed with brine dried over Na2SO4 filtered concentrated

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

実験手順: A mixture of 4.203 g (25 mmol) of ethyl 4,4,4-trifluorocrotonate, 20 mL of nitromethane and ca 0.576 g (5 mmol) of tetramethyl guanidine were stirred for 13 hours at room temperature, and then diluted with water and acidified by the addition of 0.5 M sulfuric acid. The mixture was extracted three times with diethyl ether. The combined ether extracts were washed with water, and then brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 5.601 g (98%) of 4,4,4-trifluoro-3-nitromethyl-butyric acid ethyl ester as an amber oil. The mixture was extracted three times with diethyl ether The combined ether extracts were washed with water brine, dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

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

実験手順: A mixture of 4.203 g (25 mmol) of ethyl 4,4,4-trifluorocrotonate, 20 mL of nitromethane and ca 0.576 g (5 mmol) of tetramethyl guanidine were stirred for 13 hours at room temperature, and then diluted with water and acidified by the addition of 0.5 M sulfuric acid. The mixture was extracted three times with diethyl ether. The combined ether extracts were washed with water, and then brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 5.601 g (98%) of 4,4,4-trifluoro-3-nitromethyl-butyric acid ethyl ester as an amber oil. The mixture was extracted three times with diethyl ether The combined ether extracts were washed with water brine, dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

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

実験手順: A mixture of 4.203 g (25 mmol) of ethyl 4,4,4-trifluoro-crotonate, 20 mL of nitromethane and ca. 0.576 g (5 mmol) of tetramethyl guanidine was stirred for 13 h at room temperature, and then diluted with water and acidified by the addition of 0.5 M sulfuric acid. The mixture was extracted three times with diethyl ether. The combined ether extracts were washed with water, and then brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. to give 5.601 g (98%) of 4,4,4-trifluoro-3-nitromethyl-butyric acid ethyl ester as an amber oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 (t, J=7.15 Hz, 3H) 2.76 (dd, J=6.53, 1.76 Hz, 2H) 3.61-3.84 (m, 1H) 4.13 (q, J=7.11 Hz, 2H) 4.83-5.01 (m, 2H). The mixture was extracted three times with diethyl ether The combined ether extracts were washed with water brine, dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

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

実験手順: A mixture of 4.203 g (25 mmol) of ethyl 4,4,4-trifluoro-crotonate, 20 mL of nitromethane and ca. 0.576 g (5 mmol) of tetramethyl guanidine was stirred for 13 h at room temperature, and then diluted with water and acidified by the addition of 0.5 M sulfuric acid. The mixture was extracted three times with diethyl ether. The combined ether extracts were washed with water, and then brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. to give 5.601 g (98%) of 4,4,4-trifluoro-3-nitromethyl-butyric acid ethyl ester as an amber oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 (t, J=7.15 Hz, 3H) 2.76 (dd, J=6.53, 1.76 Hz, 2H) 3.61-3.84 (m, 1H) 4.13 (q, J=7.11 Hz, 2H) 4.83-5.01 (m, 2H). The mixture was extracted three times with diethyl ether The combined ether extracts were washed with water brine, dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.0 g (5.94 mmol) of 4,4,4-trifluoro-2-butenoic acid ethyl ester and 0.15 mL (1.19 mmol) of 1,1,3,3-tetramethyl guanidine and 1.6 mL (29.8 mmol) of nitromethane were mixed. The resulting mixture was cooled to 0° C. and then stirred for 3 hours at room temperature, followed by addition of 100 mL of ethylacetoacetate. The reaction mixture was washed with water, and then an organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give 1.1 g (4.80 mmol) of the title compound in a yield of 81%. The reaction mixture was washed with water an organic layer was dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 100 mL round-bottomed flask, KOH (356 mg, 5.45 mmol) was combined with H2O (50 ml) to give a colorless solution and cooled to 0° C. 4,4,4-Trifluoro-3-nitromethyl-butyric acid ethyl ester (1.25 g, 5.45 mmol) in 10 ml THF was added and the resulting reaction mixture was stirred for 20 min. This was followed by addition of MgSO4 (657 mg, 5.45 mmol) in 5 ml of H2O then by KMnO4 (862 mg, 5.45 mmol) in 30 ml of H2O. The resulting reaction mixture was stirred for 30 min, filtered through celite and the celite cake washed with CH2Cl2. The combined filtrate and washes were washed with brine, dried over Na2SO4, filtered and concentrated to afford 4,4,4-trifluoro-3-formyl-butyric acid ethyl ester as a liquid which was used without purification. to give a colorless solution the resulting reaction mixture The resulting reaction mixture was stirred for 30 min filtered through celite the celite cake washed with CH2Cl2 The combined filtrate and washes were washed with brine dried over Na2SO4 filtered concentrated

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

実験手順: A mixture of 4.203 g (25 mmol) of ethyl 4,4,4-trifluorocrotonate, 20 mL of nitromethane and ca 0.576 g (5 mmol) of tetramethyl guanidine were stirred for 13 hours at room temperature, and then diluted with water and acidified by the addition of 0.5 M sulfuric acid. The mixture was extracted three times with diethyl ether. The combined ether extracts were washed with water, and then brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 5.601 g (98%) of 4,4,4-trifluoro-3-nitromethyl-butyric acid ethyl ester as an amber oil. The mixture was extracted three times with diethyl ether The combined ether extracts were washed with water brine, dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

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

実験手順: A mixture of 4.203 g (25 mmol) of ethyl 4,4,4-trifluoro-crotonate, 20 mL of nitromethane and ca. 0.576 g (5 mmol) of tetramethyl guanidine was stirred for 13 h at room temperature, and then diluted with water and acidified by the addition of 0.5 M sulfuric acid. The mixture was extracted three times with diethyl ether. The combined ether extracts were washed with water, and then brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. to give 5.601 g (98%) of 4,4,4-trifluoro-3-nitromethyl-butyric acid ethyl ester as an amber oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 (t, J=7.15 Hz, 3H) 2.76 (dd, J=6.53, 1.76 Hz, 2H) 3.61-3.84 (m, 1H) 4.13 (q, J=7.11 Hz, 2H) 4.83-5.01 (m, 2H). The mixture was extracted three times with diethyl ether The combined ether extracts were washed with water brine, dried over anhydrous sodium sulfate filtered concentrated under reduced pressure