Merck + Co., Inc.

Andrew L Forman

Edamanal S Venkataramani

Ralph J Magliette

Guy R Humphrey

Ross A Miller

James A McCauley

Richard Robert Dauer

Donald McKinney

William A Vaughn

Paul F McKenzie

David M Lashen

Sean R Holihan

Pascal H Toma

Disclosed is a process for recovering and recycling waste methanesulfonic acid (MSA) and phosphorous acid (H.sub.3 PO.sub.3) in a bisphosphonation process for reuse in the process. The recovery process involves treating a waste crude mother liquor stream with HCl to remove sodium ion, as sodium chloride, recovering HCl--H.sub.2 O by atmospheric distillation, separating and dehydrating a mixture of methanesulfonic acid and phosphorous acid by vacuum distillation for recycle. The substantially dry methanesulfonic acid and phosphorous acid, and previous HCl, can all be recycled back to the process for reuse.

Process for recovery and recycle of methanesulfonic acid and phosphorous

By this invention, there is provided a process for producing crystalline 4,7.beta.-dimethyl-4-aza-5.alpha.-cholestan-3-one of structural formula (I) from 4,7.beta.-dimethyl-4-aza-5.alpha.-cholestan-3-one oil. ##STR1## This crystallization process of the present invention comprises crystallization of the oil optionally containing residual solvent with vigorous but controlled agitation. Preferably, this crystallization process is carried out at select and controlled temperatures. Further, 4,7.beta.-dimethyl-4-aza-5.alpha.-cholestan-3-one has been found to exist in at least two novel polymorphic nonsolvated forms, herein referred to as Form I and Form II. Form I can be prepared pure by careful control of the crystallization process.

Process for crystallizing a 4-azasteroid 5alpha-reductase inhibitor

Disclosed is a process for removing by-product phosphorus-containing (PO.sub.x) materials, alendronate and alendronate byproducts from crude mother liquors in an omega amino-1-hydroxy-C.sub.2 -C.sub.6 alkylidene-1,1-bisphosphonic acid synthesis process, e.g. alendronate sodium. Calcium chloride is added first to the crude mother liquors, then calcium oxide to precipitate the PO.sub.x materials, then neutralized to about pH 7 to complete precipitation. Substantially all of the alendronate sodium active ingredient is removed from the precipitate. Following filtration, the PO.sub.x filtercake can then be disposed of by incineration, landfilling or reclamation of usable phosphorus as fertilizer. The remaining filtrate can then be further treated in an environmentally acceptable manner by wastewater treatment or recycling to the process.

Process for removing waste pox, alendronate and its by products

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Scotch Plains, NJ, United States of America

Andrew L Forman