1-diethoxyphosphoryl-1,1-difluoro-4-iodobutane

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

実験手順: To a solution of diethyl 1,1-difluoro-4-iodobutylphosphonate (1 eq) in DMF (0.27 M) was added sodium azide (3 eq). The reaction mixture was stirred at room temperature for 90 minutes. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was back extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-50% EtOAc/Hex to give the product as a yellowish oil. washed with water The aqueous phase was back extracted with ethyl acetate The combined organic phases were washed with brine dried over anhydrous Na2SO4 concentrated en vaccuo The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

実験手順: To a solution of diethyl 1,1-difluoro-4-iodobutylphosphonate (1 eq) in DMF (0.27 M) was added sodium azide (3 eq). The reaction mixture was stirred at room temperature for 90 minutes. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was back extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-50% EtOAc/Hex to give the product as a yellowish oil. washed with water The aqueous phase was back extracted with ethyl acetate The combined organic phases were washed with brine dried over anhydrous Na2SO4 concentrated en vaccuo The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

実験手順: To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n-butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. The mixture was then cooled down to −78° C., and diethyl difluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the reaction. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,3-diiodopropane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phase was extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil. dropwise at 0° C The mixture was then cooled down to −78° C. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution After 1.5 hours the reaction was quenched by pouring into saturated NH4Cl solution The aqueous phase was extracted with ethyl acetate three times The combined organic phases were washed with brine dried over anhydrous sodium sulfate concentrated en vaccuo The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

実験手順: To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n-butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. The mixture was then cooled down to −78° C., and diethyl difluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the reaction. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,3-diiodopropane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phase was extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil. dropwise at 0° C The mixture was then cooled down to −78° C. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution After 1.5 hours the reaction was quenched by pouring into saturated NH4Cl solution The aqueous phase was extracted with ethyl acetate three times The combined organic phases were washed with brine dried over anhydrous sodium sulfate concentrated en vaccuo The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

実験手順: To a solution of diethyl 1,1-difluoro-4-iodobutylphosphonate (1 eq) in DMF (0.27 M) was added sodium azide (3 eq). The reaction mixture was stirred at room temperature for 90 minutes. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was back extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-50% EtOAc/Hex to give the product as a yellowish oil. washed with water The aqueous phase was back extracted with ethyl acetate The combined organic phases were washed with brine dried over anhydrous Na2SO4 concentrated en vaccuo The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

実験手順: To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n-butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. The mixture was then cooled down to −78° C., and diethyl difluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the reaction. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,3-diiodopropane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phase was extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil. dropwise at 0° C The mixture was then cooled down to −78° C. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution After 1.5 hours the reaction was quenched by pouring into saturated NH4Cl solution The aqueous phase was extracted with ethyl acetate three times The combined organic phases were washed with brine dried over anhydrous sodium sulfate concentrated en vaccuo The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

実験手順: To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n-butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. The mixture was then cooled down to −78° C., and diethyl difluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the reaction. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,3-diiodopropane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phase was extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil. dropwise at 0° C The mixture was then cooled down to −78° C. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution After 1.5 hours the reaction was quenched by pouring into saturated NH4Cl solution The aqueous phase was extracted with ethyl acetate three times The combined organic phases were washed with brine dried over anhydrous sodium sulfate concentrated en vaccuo The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

実験手順: To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n-butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. The mixture was then cooled down to −78° C., and diethyl difluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the reaction. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,3-diiodopropane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phase was extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil. dropwise at 0° C The mixture was then cooled down to −78° C. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution After 1.5 hours the reaction was quenched by pouring into saturated NH4Cl solution The aqueous phase was extracted with ethyl acetate three times The combined organic phases were washed with brine dried over anhydrous sodium sulfate concentrated en vaccuo The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)