Diisopropylamine → Diethyl 1,1-difluoro-3-(2-(2-iodoethoxy)ethoxy)propylphosphonate

Temperature

0 °C

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 solution. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,2-bis(2-iodoethoxy)ethane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phases were 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.

1. customdropwise at 0° C
2. temperatureThe mixture was then cooled down to −78° C.
3. stirringThen the mixture was stirred at −78° C. for 40 minutes and to the resulting solution
4. waitAfter 1.5 hours
5. customthe reaction was quenched
6. additionby pouring into saturated NH4Cl solution
7. extractionThe aqueous phases were extracted with ethyl acetate three times
8. washThe combined organic phases were washed with brine
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated en vaccuo
11. customThe resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)

ORD record

ord-14045507e610467794d3cb36aa10ab6f

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365506B2