Study on Synthesis of Cloxacillin Sodium

In the paper,Cloxacillin Sodium,a known antibiotic,was prepared according to following procedures:2-chlorobenzaldehyde oxime(2) was prepared by oximation of 2-chlorbenzaldehyde(1) with hydroxylamine.The solution of(2) in C\-2H\-5OH was treated with Cl\-2 at 0℃.The reaction mixture was stirred with ethyl acetoacetate in hexane at room tepm.for 5h and then refluxed with agua NaOH for 2h to give 3-(2-chlorophenyl)-5-methyl-isoxazole-4-carboxylic acid(5).3-(2-chlorophyenyl)-5-methyl-isoxazole-4-carboxylic acid(5) was reflucxed with POCl\-3 and DMF for 7 h to give 3-(2-chlorophenyl-5-methylisoxazole-4-carbonyl-chloride(6).A solution of 3-(2-chlorophenyl-5-methylisoxazole-4-carbonyl-chwride(6) in 10 ml acetone was added into the suspension of 6-aminopenicilanic acid(6-APA) in 300ml water.The mixture was stirred vigorously for 60 min and butyl acetate was then added.After acidification with H\-2SO\-4 to pH2.0～2.5,the mixture became two layers.The layer of hutyl acetate was separated and the aq.layer was extraced.After adding CH 3OH,the comhinded butyl acetate-layer was treated with sodium 2-ethylhexanoate to obtain cloxacillin sodium.