Editing Loperamide (section)

== Chemistry ==
=== Synthesis ===
Loperamide is synthesized starting from the [[lactone]] 3,3-diphenyldihydrofuran-2(3H)-one and ethyl 4-oxopiperidine-1-carboxylate, on a lab scale.<ref name = "Stokbroekx_1973">{{cite journal | vauthors = Stokbroekx RA, Vandenberk J, Van Heertum AH, Van Laar GM, Van der Aa MJ, Van Bever WF, Janssen PA | title = Synthetic antidiarrheal agents. 2,2-Diphenyl-4-(4'-aryl-4'-hydroxypiperidino)butyramides | journal = Journal of Medicinal Chemistry | volume = 16 | issue = 7 | pages = 782–786 | date = July 1973 | pmid = 4725924 | doi = 10.1021/jm00265a009 }}</ref> On a large scale a similar synthesis is followed, except that the lactone and piperidinone are produced from cheaper materials rather than purchased.<ref>{{cite patent | inventor = Janssen PA, Niemegeers CJ | country = US | number = 3714159 | gdate = 1973 }}</ref><ref>{{cite patent | inventor = Janssen PA, Niemegeers CJ | country = US | number = 3884916 | gdate = 1975 }}</ref>

[[File:Loperamide synthesis.png|class=skin-invert-image|thumb|375px|Synthetic route to Loperamide.]]

=== Physical properties ===
Loperamide is typically manufactured as the hydrochloride salt. Its main [[Polymorphism (materials science)|polymorph]] has a [[melting point]] of 224&nbsp;°C and a second polymorph exists with a melting point of 218&nbsp;°C. A [[Hydrate|tetrahydrate]] form has been identified which melts at 190&nbsp;°C.<ref>{{cite journal | vauthors = Van Rompay J, Carter JE | title = Loperamide hydrochloride. | journal = Analytical Profiles of Drug Substances | date = January 1990 | volume = 19 | pages = 341–365 | publisher = Academic Press | veditors = Florey K |doi=10.1016/s0099-5428(08)60372-x| isbn = 9780122608193 }}</ref>