Methyl-2-N-(acetylamino)-dimethyl phosphono acetate

Uses

Trimethyl α-(Acetamido)phosphonoacetate can be prepared to use as HDAC inhibitor to treat cell proliferative diseases, autoimmune diseases, inflammation, neurodegenerative diseases or viral diseases.

Synthesis

GENERAL STEPS: Compound C152 (12.65 g, 38.2 mmol) and acetic anhydride (9.02 mL, 95.5 mmol) were dissolved in methanol (100 mL), and the mixed solution was transferred to a Parr autoclave. 10% Pd/C catalyst (0.640 g) was added and the hydrogenation reaction was carried out at 45 psi hydrogen pressure for 3 hours. Upon completion of the reaction, the catalyst was removed by filtration and the filtrate was concentrated under reduced pressure to give an oil. The oil was placed in a depressurized environment and reduced pressure was applied to solidify it. The resulting white solid was dissolved in a small amount of ethyl acetate and pentane was slowly added with vigorous stirring until a precipitate began to form. The precipitate was separated by filtration to give methyl 2-acetamido-2-(dimethoxyphosphoryl)acetate (C153) as a white powder in 87% yield. Mass spectrometry (chemical ionization, CI) analysis showed a molecular ion peak (M+H)+ m/z of 240 for C7H14NO6P.

References

[1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 8, p. 1277 - 1286
[2] Synthesis, 1984, # 1, p. 53 - 60
[3] Organic Syntheses, 2011, vol. 88, p. 152 - 161
[4] Tetrahedron, 2007, vol. 63, # 51, p. 12740 - 12746
[5] Patent: WO2004/39815, 2004, A2. Location in patent: Page 52 - 53