Laboratory Synthesis Of Carprofen

Carprofen Synthesis

Use: non-steroidal anti-inflammatory

MW: 273.72

LD 50: 400 mg/kg (M, p.o.)

method of synthesis

cyclohexenone (I) is condensed with diethyl methyl malonate (II) gives diethyl -methyl-(3-oxocyclohexanyl)malonate (III) which is hydrolyzed and decarboxylated with refluxing dioxane-HCl to yield alpha-methyl-3-oxocyclohexaneacetic acid (IV), oil, b.p.(0.7) = 164-6 C, n(20)(D) = 1.4794. The condensation of (IV) with 4-chlorophenylhydrazine (A) in acetic acid-water atfords 6-chloro-alpha-methyl-1,2,3,4-tetrahydrocarbazole-2-acetic acid (V), which is esterified with ethanol-HCl to ethyl 6-chloro-alpha-methyl-1,2,3,4-tetrahydrocarbazole-2-acetate (VI) and aromatized with chloranil (B) in refluxing xylene to give ethyl 6-chloro-alpha-methylcarbazole-2-acetate (VII)Finally, this ester is hydrolyzed with NaOH in refluxing ethanol

reference

• Drugs Fut1977,2,(1):15
• US patent 3896145