diethyl 2-(4,4,4-trifluorobutanoyl)propanedioate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 20.35 g of magnesium (turning) and 148 ml of ethanol, 0.1 ml of carbon tetrachloride was added and heated to 55° C. To the mixture, a mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added dropwise over one hour. After 2 hours, the reaction solution was cooled to -5° C. under a nitrogen flow and 112 g of 4,4, 4-trifluorobutyryl chloride was added. After the temperature was returned to ambient temperature over one hour, the reaction was further conducted for 12 hours. The reaction solution was poured into an aqueous 5% ice-cooled hydrochloric acid, and extracted three times with diethyl ether. The layers were combined and the combined ether layer was washed twice with saturated 20 saline and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to give 179 g of 4,4,4-trifluorobutyryl-malonic acid diethyl ester (b.p.: 125°-134° C., 15 mmHg) (yield: 90%). 1H-NMR (CDCl3, internal standard TMS); δ value (ppm): 1.32 (t, 3H), 2.50 (m, 2H), 2.95 (t, 2H), 4.29 (q, 2H), 4.50 (s, 1H) was added was added After the temperature was returned to ambient temperature over one hour the reaction was further conducted for 12 hours extracted three times with diethyl ether the combined ether layer was washed twice with saturated 20 saline dried over anhydrous magnesium sulfate Then, the solvent was distilled off under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.1 ml of carbon tetrachloride was added to a mixture of 20.35 g of magnesium(turnings) and 148 ml of ethanol and then heated at 55° C. A mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added to the reaction mixture over 1 hour. Two hours later the reaction solution was cooled to -5° C. and 112 g of 4,4,4-trifluorobutyryl chloride was added to the solution under an atmosphere of nitrogen, then the resultant reaction mixture was left at an ambient temperature for 1 hour. Then the mixture was allowed to react further 12 hours. After completion of the reaction, the reaction solution was poured into a 5% hydrochloric acid solution and extracted three times with diethyl ether. The ether layers were combined and washed twice with brine and dried over anhydrous magnesium sulfate. The filtered ether solution was evaporated under reduced pressure. The obtained residue was distilled under reduced pressure to yield 179 g of the desired 4,4,4-trifluoro-butyrylmalonic acid diethyl ester in a yield of 90%. Two hours later the reaction solution was cooled to -5° C. the resultant reaction mixture to react further 12 hours After completion of the reaction extracted three times with diethyl ether washed twice with brine dried over anhydrous magnesium sulfate The filtered ether solution was evaporated under reduced pressure The obtained residue was distilled under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.1 ml of carbon tetrachloride was added to a mixture of 20.35 g of magnesium(turnings) and 148 ml of ethanol and then heated at 55° C. A mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added to the reaction mixture over 1 hour. Two hours later the reaction solution was cooled to -5° C. and 112 g of 4,4,4-trifluorobutyryl chloride was added to the solution under an atmosphere of nitrogen, then the resultant reaction mixture was left at an ambient temperature for 1 hour. Then the mixture was allowed to react further 12 hours. After completion of the reaction, the reaction solution was poured into a 5% hydrochloric acid solution and extracted three times with diethyl ether. The ether layers were combined and washed twice with brine and dried over anhydrous magnesium sulfate. The filtered ether solution was evaporated under reduced pressure. The obtained residue was distilled under reduced pressure to yield 179 g of the desired 4,4,4-trifluoro-butyrylmalonic acid diethyl ester in a yield of 90%. Two hours later the reaction solution was cooled to -5° C. the resultant reaction mixture to react further 12 hours After completion of the reaction extracted three times with diethyl ether washed twice with brine dried over anhydrous magnesium sulfate The filtered ether solution was evaporated under reduced pressure The obtained residue was distilled under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 20.35 g of magnesium (turning) and 148 ml of ethanol, 0.1 ml of carbon tetrachloride was added and heated to 55° C. To the mixture, a mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added dropwise over one hour. After 2 hours, the reaction solution was cooled to -5° C. under a nitrogen flow and 112 g of 4,4, 4-trifluorobutyryl chloride was added. After the temperature was returned to ambient temperature over one hour, the reaction was further conducted for 12 hours. The reaction solution was poured into an aqueous 5% ice-cooled hydrochloric acid, and extracted three times with diethyl ether. The layers were combined and the combined ether layer was washed twice with saturated 20 saline and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to give 179 g of 4,4,4-trifluorobutyryl-malonic acid diethyl ester (b.p.: 125°-134° C., 15 mmHg) (yield: 90%). 1H-NMR (CDCl3, internal standard TMS); δ value (ppm): 1.32 (t, 3H), 2.50 (m, 2H), 2.95 (t, 2H), 4.29 (q, 2H), 4.50 (s, 1H) was added was added After the temperature was returned to ambient temperature over one hour the reaction was further conducted for 12 hours extracted three times with diethyl ether the combined ether layer was washed twice with saturated 20 saline dried over anhydrous magnesium sulfate Then, the solvent was distilled off under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.1 ml of carbon tetrachloride was added to a mixture of 20.35 g of magnesium(turnings) and 148 ml of ethanol and then heated at 55° C. A mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added to the reaction mixture over 1 hour. Two hours later the reaction solution was cooled to -5° C. and 112 g of 4,4,4-trifluorobutyryl chloride was added to the solution under an atmosphere of nitrogen, then the resultant reaction mixture was left at an ambient temperature for 1 hour. Then the mixture was allowed to react further 12 hours. After completion of the reaction, the reaction solution was poured into a 5% hydrochloric acid solution and extracted three times with diethyl ether. The ether layers were combined and washed twice with brine and dried over anhydrous magnesium sulfate. The filtered ether solution was evaporated under reduced pressure. The obtained residue was distilled under reduced pressure to yield 179 g of the desired 4,4,4-trifluoro-butyrylmalonic acid diethyl ester in a yield of 90%. Two hours later the reaction solution was cooled to -5° C. the resultant reaction mixture to react further 12 hours After completion of the reaction extracted three times with diethyl ether washed twice with brine dried over anhydrous magnesium sulfate The filtered ether solution was evaporated under reduced pressure The obtained residue was distilled under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 20.35 g of magnesium (turning) and 148 ml of ethanol, 0.1 ml of carbon tetrachloride was added and heated to 55° C. To the mixture, a mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added dropwise over one hour. After 2 hours, the reaction solution was cooled to -5° C. under a nitrogen flow and 112 g of 4,4,4-trifluorobutyryl chloride was added. After the temperature was returned to ambient temperature over one hour, the reaction was further conducted for 12 hours. The reaction solution was poured into an aqueous 5% ice-cooled hydrochloric acid, and extracted three times with diethyl ether. The layers were combined and the combined ether layer was washed twice with saturated saline and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to give 179 g of 4,4,4-trifluorobutyryl-malonic acid diethyl ester (b.p.: 125°-134° C., 15 mmHg) (yield: 90%). was added was added After the temperature was returned to ambient temperature over one hour the reaction was further conducted for 12 hours extracted three times with diethyl ether the combined ether layer was washed twice with saturated saline dried over anhydrous magnesium sulfate Then, the solvent was distilled off under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 20.35 g of magnesium (turning) and 148 ml of ethanol, 0.1 ml of carbon tetrachloride was added and heated to 55° C. To the mixture, a mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added dropwise over one hour. After 2 hours, the reaction solution was cooled to -5° C. under a nitrogen flow and 112 g of 4,4,4-trifluorobutyryl chloride was added. After the temperature was returned to ambient temperature over one hour, the reaction was further conducted for 12 hours. The reaction solution was poured into an aqueous 5% ice-cooled hydrochloric acid, and extracted three times with diethyl ether. The layers were combined and the combined ether layer was washed twice with saturated saline and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to give 179 g of 4,4,4-trifluorobutyryl-malonic acid diethyl ester (b.p.: 125°-134° C., 15 mmHg) (yield: 90%). was added was added After the temperature was returned to ambient temperature over one hour the reaction was further conducted for 12 hours extracted three times with diethyl ether the combined ether layer was washed twice with saturated saline dried over anhydrous magnesium sulfate Then, the solvent was distilled off under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.1 ml of carbon tetrachloride was added to a mixture of 20.35 g of magnesium(turnings) and 148 ml of ethanol and then heated at 55° C. A mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added to the reaction mixture over 1 hour. Two hours later the reaction solution was cooled to -5° C. and 112 g of 4,4,4-trifluorobutyryl chloride was added to the solution under an atmosphere of nitrogen, then the resultant reaction mixture was left at an ambient temperature for 1 hour. Then the mixture was allowed to react further 12 hours. After completion of the reaction, the reaction solution was poured into a 5% hydrochloric acid solution and extracted three times with diethyl ether. The ether layers were combined and washed twice with brine and dried over anhydrous magnesium sulfate. The filtered ether solution was evaporated under reduced pressure. The obtained residue was distilled under reduced pressure to yield 179 g of the desired 4,4,4-trifluorobutyrylmalonic acid diethyl ester in a yield of 90%. (b.p. 125°-134° C., 15 mmHg) Two hours later the reaction solution was cooled to -5° C. the resultant reaction mixture to react further 12 hours After completion of the reaction extracted three times with diethyl ether washed twice with brine dried over anhydrous magnesium sulfate The filtered ether solution was evaporated under reduced pressure The obtained residue was distilled under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 20.35 g of magnesium (turning) and 148 ml of ethanol, 0.1 ml of carbon tetrachloride was added and heated to 55° C. To the mixture, a mixed solution of 197 ml of ethanol, 700 ml of diethyl ether and 168 g of diethyl malonate was added dropwise over one hour. After 2 hours, the reaction solution was cooled to -5° C. under a nitrogen flow and 112 g of 4,4, 4-trifluorobutyryl chloride was added. After the temperature was returned to ambient temperature over one hour, the reaction was further conducted for 12 hours. The reaction solution was poured into an aqueous 5% ice-cooled hydrochloric acid, and extracted three times with diethyl ether. The layers were combined and the combined ether layer was washed twice with saturated 20 saline and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to give 179 g of 4,4,4-trifluorobutyryl-malonic acid diethyl ester (b.p.: 125°-134° C., 15 mmHg) (yield: 90%). 1H-NMR (CDCl3, internal standard TMS); δ value (ppm): 1.32 (t, 3H), 2.50 (m, 2H), 2.95 (t, 2H), 4.29 (q, 2H), 4.50 (s, 1H) was added was added After the temperature was returned to ambient temperature over one hour the reaction was further conducted for 12 hours extracted three times with diethyl ether the combined ether layer was washed twice with saturated 20 saline dried over anhydrous magnesium sulfate Then, the solvent was distilled off under reduced pressure