Separation of triphenylphosphine oxide from methotrexate ester and purification of said ester

• Main Authors: WEBSTER; JAMES A, ELLARD; JAMES A
• Format: Patent
• Language: English
• Published: 20.12.1983
• Subjects: CHEMISTRY; CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION ORPROCESSING OF GOODS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS; TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINSTCLIMATE CHANGE

An improvement in the production of methotrexate as set out in Ellard U.S. Pat. No. 4,080,325. It has been found that magnesium oxide facilitates the coupling reaction by acting as an acid acceptor. The dense grade of magnesium oxide is preferred in molar proportions of 2 to 4 moles of magnesium oxide per mole of 2,4-diamino-6-hydroxymethylpteridine. Further, the triphenylphosphine oxide which is generated by hydrolysis of the protecting groups is removed from the reaction stream by utilization of toluene or BTX-type solvents.