Patent EA-003861-B1 (EA)
Title: Novel process for preparing alendronic acid
Inventor: LIDOR-HADAS RAMY
IPC: A61P19/08
Filed: 2000-02-11
Abstract: 1. A process for the preparation of alendronic acid, which comprises the steps of: a) reacting a compound of the formula I with H3PO3 wherein R is an imido group; and R<1> is selected from the group which consists of chloro, bromo, iodo, fluoro, hydroxy, amino,-OR<2> or-OC (O)R<2>, wherein R<2> is C1-C12 alkyl, C1-C12 cycloalkyl, or C1-C12 aryl; b) reacting the product of step (a) with a deprotecting agent; and c) recovering alendronic acid. 2. A process according to claim 1 wherein R is selected from the group, which consists of N-phthalimido and N-maleimido. 3. A process according to claim 1 wherein R<1> is selected from the group which consists of chloro, bromo and hydroxy. 4. A process according to claim 1 wherein step (a) further comprises the use of one or more of the compounds selected from the group, which consists of H3PO4, PCl3, PCl5 and POCl3. 5. A process according to claim 1 wherein step (b) comprises using one or more deprotecting agents selected from the group which consists of HCl, HBr, acetic acid, H3PO3, and H3PO4. 6. A process according to claim 1, wherein steps (a) and (b) take place in a single vessel. 7. A process according to claim 1 in which step (a) is performed at the temperature of between about 25 degree C and about 180 degree C. 8. A process according to claim 7 in which step (a) is performed at the temperature of between about 80 degree and about 140 degree C. 9. A process according to claim 1 in which step (b) is performed at the temperature of between about 25 degree C and about 130 degree C. 10. A process according to claim 9 in which step (b) is performed at the temperature of between about 100 degree C and about 130 degree C. 11. A process according to claim 6, which is, performed at the temperature of between about 25 degree C and about 180 degree C. 12. A process according to claim 11, which is, performed at the temperature of between about 80 degree C and about 140 degree C. 13. A process according to claim 1 wherein the molar ratio between the compound of formula I and H3PO3 is between 1: 1 and 1: 6. 14. A process according to claim 13 wherein the molar ratio between the compound of formula I and H3PO3 is between 1: 2 and 1: 5. 15. A process according to claim 4 wherein the molar ratio between the compound of formula I and PCl3 is between 1: 1 and 1: 6. 16. A process according to claim 15 wherein the molar ratio between the compound of formula I and PCl3 is between 1: 2 and 1: 3. 17. A process according to claim 4 wherein the molar ratio between the compound of formula I and H3PO4 is between 1: 1 and 1: 6. 18. A process according to claim 17 wherein the molar ratio between the compound of formula I and H3PO4 is between 1: 2 and 1: 4. 19. A process according to claim 4 wherein the molar ratio between the compound of formula I and PCl5 is between 1: 1 and 1: 6. 20. A process according to claim 19 wherein the molar ratio between the compound of formula I and PC5 is between 1: 2 and 1: 3. 21. A process according to claim 4 wherein the molar ratio between the compound of formula I and POC3 is between 1: 1 and 1: 6. 22. A process according to claim 21 wherein the molar ratio between the compound of formula I and POC3 is between 1: 2 and 1: 3.