diethyl 2,2-difluoropentanedioate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl bromodifluoroacetate (33.2 g) in tetrahydrofuran (94.0 g) was added ethyl acrylate (8.2 g) and copper powder (10.9 g). After heating to 50° C., TMEDA (9.5 g) was added dropwise and the reaction mixture was then stirred for 3 hours at the same temperature. Upon disappearance of ethyl acrylate as the starting material, to the reaction solution was added methyl t-butyl ether (MTBE, 73.7 g) followed by addition of 10% aqueous ammonium chloride solution (49.8 g) dropwise, and the mixture was then stirred for 30 minutes. The remaining copper residue was removed by filtration through a celite, and methyl t-butyl ether (MTBE, 66.3 g) was added to separate the layers. The separated organic layer was washed successively with 10% aqueous NH4Cl solution (66.3 g) and 3 N aqueous hydrochloric acid solution (99.6 g) in order and then distilled under reduced pressure to obtain 55.0 g of the desired title compound. the mixture was then stirred for 30 minutes The remaining copper residue was removed by filtration through a celite, and methyl t-butyl ether (MTBE, 66.3 g) was added to separate the layers The separated organic layer was washed successively with 10% aqueous NH4Cl solution (66.3 g) and 3 N aqueous hydrochloric acid solution (99.6 g) in order distilled under reduced pressure

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl bromodifluoroacetate (33.2 g) in tetrahydrofuran (94.0 g) was added ethyl acrylate (8.2 g) and copper powder (10.9 g). After heating to 50° C., TMEDA (9.5 g) was added dropwise and the reaction mixture was then stirred for 3 hours at the same temperature. Upon disappearance of ethyl acrylate as the starting material, to the reaction solution was added methyl t-butyl ether (MTBE, 73.7 g) followed by addition of 10% aqueous ammonium chloride solution (49.8 g) dropwise, and the mixture was then stirred for 30 minutes. The remaining copper residue was removed by filtration through a celite, and methyl t-butyl ether (MTBE, 66.3 g) was added to separate the layers. The separated organic layer was washed successively with 10% aqueous NH4Cl solution (66.3 g) and 3 N aqueous hydrochloric acid solution (99.6 g) in order and then distilled under reduced pressure to obtain 55.0 g of the desired title compound. the mixture was then stirred for 30 minutes The remaining copper residue was removed by filtration through a celite, and methyl t-butyl ether (MTBE, 66.3 g) was added to separate the layers The separated organic layer was washed successively with 10% aqueous NH4Cl solution (66.3 g) and 3 N aqueous hydrochloric acid solution (99.6 g) in order distilled under reduced pressure

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

実験手順: 2,2-difluoropentanedioic acid diethyl ester (21 g) synthesized in Section (1) was dissolved in ethanol (50 mL) and 2.0 M methanolic ammonia was slowly added thereto. The mixture was stirred at room temperature for 30 min and distilled under reduced pressure to afford 18.2 g of the title compound as viscous oil, which was used in the subsequent step without further purification. distilled under reduced pressure

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

実験手順: Commercially available ethyl bromodifluoroacetate (16 mL, 120 mmol) and ethyl acrylate (11 mL, 100 mmol) were dissolved in tetrahydrofuran (100 mL), and copper powder (15.2 g, 240 mmol) and TMEDA (16.7 mL, 110 mmol) were sequentially added thereto at room temperature. After stirring for about 8 hours, the reaction was terminated by the addition of a saturated aqueous solution of 1.0 N hydrochloric acid and was extracted two times with toluene. The reaction solution was distilled under reduced pressure and the concentrated title compound was directly used in the subsequent step without further purification. at room temperature the reaction was terminated by the addition of a saturated aqueous solution of 1.0 N hydrochloric acid was extracted two times with toluene The reaction solution was distilled under reduced pressure the concentrated title compound was directly used in the subsequent step without further purification

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl bromodifluoroacetate (33.2 g) in tetrahydrofuran (94.0 g) was added ethyl acrylate (8.2 g) and copper powder (10.9 g). After heating to 50° C., TMEDA (9.5 g) was added dropwise and the reaction mixture was then stirred for 3 hours at the same temperature. Upon disappearance of ethyl acrylate as the starting material, to the reaction solution was added methyl t-butyl ether (MTBE, 73.7 g) followed by addition of 10% aqueous ammonium chloride solution (49.8 g) dropwise, and the mixture was then stirred for 30 minutes. The remaining copper residue was removed by filtration through a celite, and methyl t-butyl ether (MTBE, 66.3 g) was added to separate the layers. The separated organic layer was washed successively with 10% aqueous NH4Cl solution (66.3 g) and 3 N aqueous hydrochloric acid solution (99.6 g) in order and then distilled under reduced pressure to obtain 55.0 g of the desired title compound. the mixture was then stirred for 30 minutes The remaining copper residue was removed by filtration through a celite, and methyl t-butyl ether (MTBE, 66.3 g) was added to separate the layers The separated organic layer was washed successively with 10% aqueous NH4Cl solution (66.3 g) and 3 N aqueous hydrochloric acid solution (99.6 g) in order distilled under reduced pressure