Cloxacillin Sodium

C19H17ClN3NaO5S3H2O
MW 475.9
Action and use:
Penicillin antibacterial
 Cloxacillin sodium: synthesis

Kar A. Medicinal Chemistry, 4th ed. New Delhi: New Age International;2007.
 Impurities

3-(2-chlorophenyl)- 6-aminopenicillanic acid

5-methylisoxazole- (6-APA)
4-carboxylic acid

Kar A. Medicinal Chemistry, 4th ed. New Delhi: New Age International;2007.
 Impurities

COOH
CH3
Cloxacillin 6-APA H
CH3

N
S
O

CH3 HN H

O O O
O
C N
N CH3
HN

H S CH3
H
Cl

6-APA cloxacillin amide

Kar A. Medicinal Chemistry, 4th ed. New Delhi: New Age International;2007.

Impurities
H
CH3 COONa
O
O
N CH3
C
Residual NaOH
O
CH3
N S
N H
H H

Cloxacillin Sodium
Cl

Penicilloic acid of Cloxacillin

H COOH

Alkali hydrolysis CH3 CH3

O HN CH3
O
C S
N
HN

H
Cl

Penilloic acid of Cloxacillin

+ CO2
 Synthesis

HCl + SO2

Vardanyan RS, Hruby VJ. Synthesis of Essential Drugs. Elsevier;2007.

 Impurities
• N,N-Dimethylaniline:
– To abstract HCl
• The presence of HCl
inhibits the synthesis
– High boiling point
(192-194 °C)
• Not been fully
elucidated Maximum 20 ppm
– Possible
carcinogenicity

Choi JK, Park MK. Arch. Pharm. Res. 1981; 4(2):85-90.