Industrial process for the synthesis of 2-substituted 1-(hydroxy-ethylidene)-1,1-bisphosfi- conic acids of high purity and the salts thereof

A process for preparing a compound of the Formula (I)

• or a hydrate or a pharmaceutically acceptable salt or hydrate thereof in a purity of >99.9%, wherein
• R is 3′-pyridyl or 2′-amino-ethylidene, which comprises the step of:
• phosphonylating a compound of the Formula (II)
• R—CH2—COOH
• or a pharmaceutically acceptable salt or hydrate thereof in a reaction mixture with a chlorine-free phosphonylating agent comprising phosphorous acid in the presence of methanesulfonic acid and phosphorous pentoxide to obtain the compound of the Formula (I) or a hydrate thereof;
• and in the case where a pharmaceutically acceptable salt of the compound of the Formula (I) is desired, reacting the compound of the Formula (I) with a base.