Methyl diethylphosphonoacetate

Chemical Properties

Clear colorless to slightly yellow liquid

Uses

Methyl diethylphosphonoacetate is used as a reagent in the preparation of allylic fluorides compounds and in regioselective Diels-Alder reactions. It also serves as a reactant in the preparation of substituted thiophenes and furans, which finds application in type 2 diabetes treatment. Further, it acts as a precursor in the synthesis of pyridone alkaloids and immunosuppressive cyclopentanediol derivatives. In addition to this, it is utilized in the modification of botulinum neurotoxin serotype A protease inhibitors.

reaction suitability

reaction type: C-C Bond Formation

Synthesis

TMSBr (90 μL, 0.691 mmol) was added to a solution of anhydrous CH2Cl2 (0.55 mL) of trimethyl phosphonoacetate (2; 50.3 mg, 0.276 mmol) at room temperature. After the reaction mixture was stirred under argon protection at room temperature for 5 h, the solvent was removed by vacuum evaporation to afford methyl 2-[bis[(trimethylmethylsilyl)oxy]phosphono}acetate (4), which was used for the next reaction without further purification. Subsequently, Ph3P (181 mg, 0.691 mmol) and I2 (175 mg, 0.691 mmol) were added to an anhydrous CHCl3 (1.8 mL) solution of 4 under argon protection. The reaction mixture was stirred at room temperature for 15 minutes and then imidazole (188 mg, 2.76 mmol) was added. Stirring was continued at room temperature for 15 minutes, then the reaction mixture was heated to 50°C and held for 30 minutes. Next, 2,2,2-trifluoroethanol (79 μl, 1.10 mmol) was added and the reaction mixture was stirred at 60°C for 5 hours. Upon completion of the reaction, the reaction mixture was filtered and the filtrate was evaporated under vacuum to give the crude product 1. The crude product was purified by column chromatography [silica gel PSQ 60B: n-hexane-EtOAc (2:1)] to give the final product methyl diethylphosphonoacetate (1; 82.3 mg, 94%) as a colorless oil.

References

[1] Synlett, 2018, vol. 29, # 11, p. 1461 - 1464