帕米膦酸酯的制备与表征

Synthesis and characterization of pamidronate bisphosphonate tetramethylesters

以Fmoc-β-丙氨酸为原料,通过Michaelis-Arbuzov反应一锅法合成了Fmoc-β-丙氨酰双膦酸甲酯,再通过四丁基氟化铵(TBAF)常温下脱去Fmoc保护基,得到纯品帕米膦酸酯。分别使用核磁共振、电喷雾质谱、红外光谱及元素分析对产物进行了表征。此方法原料廉价易得、反应条件温和、副产物较少、且易于分离纯化,提供了一种合成高纯度双膦酸酯类化合物的方法。

（ 9H-fluoren-9-yl） methyl（ 3,3-bis（ dimethoxyphosphoryl）-3-hydroxypropyl） carbamate（ 3）was obtained in good yield through a one-pot procedure by Michaelis-Arbuzov reaction starting from Fmoc-β-alanine. To gain the final product,weak basic tetra-n-butylammonium fluoride（ TBAF） was used to remove the Fmoc group. The structures of the two compounds were characterized by 1H NMR,13C NMR,31P NMR,ESI-MS,IR spectra and elemental analysis. The title compound was achieved with cheap raw materials,mild-conditions and simple-operation. The methods for isolation and purification of the title compound were relatively simple. It provided an efficient method for the synthesis of high-purity bisphosphonic esters.