Synthesis
The synthesis method of Bis(2,2,2-trifluoroethyl) (Methoxycarbonylmethyl) phosphonate is as follows: To a stirred solution of dried 18-crown-6 (4.53 g, 17.14 mmol), THF (20 mL),
and Bis(2,2,2-trifluoroethyl) Phosphite (0.70 mL, 1.29 mmol), was added KHMDS (9.0 mL, 4.50 mmol, 0.5M in
toluene) by syringe in a dropwise manner at -78 ℃. After 15 min, methyl chloroacetate
(0.30 mL, 3.41 mmol) was added and the reaction mixture was allowed to stir for 4 hr at
room temperature. The reaction mixture was diluted with EtOAc (20 mL) and then
quenched with sat. ammonium chloride (50 mL). The aqueous layer was extracted with
EtOAc (3 x 30 mL). The combined organic extracts were dried under anhydrous
magnesium sulfate. Following filtration, the solvents were removed in vacuo. The crude
product was then purified by flash column chromatography (33% EtOAc in hexanes, Rf =
0.22 in 33% EtOAc in hexanes) yielding Bis(2,2,2-trifluoroethyl) (Methoxycarbonylmethyl)phosphonate (766 mg, 2.41 mmol, 70.3%)
as a yellow syrup.
