Patent ID: 8026388

Claim:
A process of making a biphosphonate, which comprises: reacting in a solvent/diluent a carboxylic acid compound of formula (2) or a salt thereof Z—COOH (2), wherein Z represents a C1-C6 alkyl group optionally substituted by an amino group, one or two C1-C6 alkylamino group(s), or a nitrogen-containing heterocyclic group, with a phosphonation agent to form cyclic pyrophosphonate intermediates, wherein said solvent/diluent comprises at least one compound of formula (3) wherein R is hydrogen or a C1-C6 alkyl group; each of R1 is a C1-C6 alkyl group or both R1 groups are linked to form a C1-C3 alkylene group; and R2 is hydrogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, or is linked together with R to form a C3-C7 carbon ring; and hydrolyzing said cyclic pyrophosphonate intermediates to form a compound of formula (1) or a salt or hydrate thereof wherein Z is as defined above.