Loperamide HCl
4-(4-chlorophenyl)-4-hydroxy-N,N-dimethyl-,-diphenyl-1-piperidinebutanamide monohydrochloride
CAS-34552-83-5
4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl-,-diphenyl-1-piperidinebutyranamide
monohydrochloride
CH3
CH3 N
O
C
C CH2CH2 N
OH
.HCl
Cl
C29H33ClN2O2.HCl
MW 477.04+36.46= 513.50
Loperamide is an antidiarrheal synthesized in 1969 in the lab. of Janssen Pharmaceutica, Beerse,
Belgium.
The Janssen synthesis of loperamide HCl is detailed in Fig.1. -(2-Bromoethyl)-phenylbenzeneacetonitrile is converted through a series of reactions to N-[dihydro-3,3-diphenyl-2(3H)furanylidene-N-methyl methanaminium bromide and ethyl 4-oxo-1-piperidinecarboxylate is converted to
4-(4-chlorophenyl)-4-piperidinol. The condensation of the basic piperidine nitrogen with furanylidene
results in the formation of loperamide base, which is then crystallized as the hydrochloride salt.
Recrystallization has resulted in the identification of two polymorphs and a tetrahydrate form.
Fig.1 Synthetic pathway of loperamide
CN
C CH2 CH2Br
C2H5OOC N
O
Cl
Cl
CH3COOH
Mg
O
O
OH
C2H5OOC N
Cl
HBr
OH
COOH
C CH2 CH2Br
HN
Cl
SOCl2
NH(CH3)2
CH3
CH3 N
O
OH
Br
HN
Cl
CH3
CH3
N
O
C
OH
C CH2CH2 N
Cl
LOPERAMIDE
HCl salt