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)-5-methylisoxazole-4-carboxylic acid

6-aminopenicillanic acid (6-APA)

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

Impurities

Cl

N

O

CH3

C

O

HN

N

O

S

CH3

CH3HH

HN

N

OS

COOH CH3

CH3

H

H

H

O

Cloxacillin 6-APA

6-APA cloxacillin amide

Impurities

Cl

N

O

CH3

C

O

NH

N

O

S

COONa

CH3

CH3

H

H H

Residual NaOH

Cloxacillin Sodium

Penicilloic acid of Cloxacillin

Cl

N

O

CH3

C

O

HN

HN

S

COOH

CH3

CH3

H

H

Penilloic acid of Cloxacillin

Alkali hydrolysis

+ CO2

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

Synthesis

HCl + SO2

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

Impurities

• N,N-Dimethylaniline:– To abstract HCl

• The presence of HClinhibits the synthesis

– High boiling point (192-194 °C)

• Not been fully elucidated

– Possible carcinogenicity

Maximum 20 ppm

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