5187-94-0

Upstream product

• 551-16-6 6-Aminopenicillanic Acid 
• 18297-63-7 N,N'-bis(trimethylsilyl)urea 
• 5321-31-3 phenylglycidylchloride hydrochloride 
• 57397-48-5 N,N-Bis(trimethylsilyl)urea 
• 554-68-7 triethylamine hydrochloride 
• 74221-76-4 ampicillin (3-phthalidylidene)ethyl ester hydrochloride 
• 551-16-6 6-aminopenicillanic acid 
• 75-78-5 dimethylsilicon dichloride 
• 108-10-1 4-methyl-2-pentanone 
• 744949-71-1 D-(-)-α-phenylglycylchloride 

Downstream Products

• 88238-54-4 ampicillin (5,7-dimethoxyisocoumarin-4-yl)-methyl ester hydrochloride 
• 88270-99-9 ampicillin (3-(6-chlorophthalidylidene))ethyl ester hydrochloride 
• 88271-00-5 ampicillin (3-(6-methoxyphthalidylidene))ethyl ester hydrochloride 
• 88238-53-3 ampicillin (3-(2-thiophthalidylidene))ethyl ester hydrochloride 
• 74221-76-4 ampicillin (3-phthalidylidene)ethyl ester hydrochloride 
• 75018-01-8 (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 2-[3-oxo-3H-isobenzofuran-(1Z)-ylidene]-ethyl ester 
• 5146-41-8 (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(5-oxo-2,4-diphenyl-imidazolidin-1-yl)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 
• 1256-08-2 (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 

Relevant academic research and scientific papers

Silylation process

A process for the silylation of 6-aminopenicillanic acid or 7-amino-desacetoxy-cephalosporanic acid by silylation in certain carboxylic acid esters and its use in the production of 6-alpha-aminoacyl-penicillins and 7-alpha-aminoacyl-desacetoxy-cephalosporins.

Beta lactam production

A new process is described for the production of 6-alpha-amino-penicillins and 7-alpha-amino-desacetoxy-cephalosporins free from halogen-containing solvents by acylating 6-APA, 7-ADCA or a derivative thereof in a halogen-free solvent.

Pharmaceutical tablet, pharmaceutical granulate and process for their preparation

A pharmaceutical tablet containing an amphoteric beta-lactam antibiotic, microcrystalline or micro fine cellulose or a mixture of both and a second disintegrant, being low-substituted hydroxypropylcellulose, which fully disintegrates in water within 60 seconds. When swallowed it shows a bioavailability as good as a pharmacy prepared suspension of the antibiotic. The tablet is compressed from a mixture containing a new granulate which is prepared from the antibiotic substance, microcrystalline and/or micro fine cellulose and water only. Such tablets can also be prepared by using other known tablet disintegrants as the second disintegrant.

Manufacture of semi-synthetic penicillin antibiotics

Improvements in or relating to the manufacture of semi-synthetic penicillin antibiotics are described. More particularly an improved process for the preparation of a 6β-acylamino penicillanic acid antibiotic product is described in which 6β-aminopenicillanic acid (6-APA) is reacted in an inert solvent with a silylating agent to form a silylated compound of formula (I) STR1 wherein R1 represents a hydrogen atom or a tri(C1-6 alkyl)silyl group, and R2 represents a tri(C1-6 alkyl)silyl group and the compound of formula (I) is thereafter contacted with an acyl chloride or protected acyl chloride corresponding to the desired 6β-acylamino group, the silyl groups are cleaved and the desired antibiotic product is recovered, silylation being effected using a tri(C1-6 alkyl) silylurea or tri(C1-6 alkyl) halosilane and the compound of formula (I) produced being reacted without intermediate isolation with the acyl chloride or protected acyl chloride, wherein acylation is effected in the presence of a hydrogen halide acceptor mixture comprising in excess of 0.15 and preferably up to 3.00 moles of urea per mole of 6-APA; in excess of 0.15, and preferably up to 1.30 moles of bis-tri-(C1-6 alkyl)silylurea per mole of 6-APA; and in excess of 0.25, and preferably up to 3.30 moles of tri-(C1-6 alkyl)-ammonium halide per mole of 6-APA. The process is especially useful for the preparation of ampicillin and amoxycillin in high yield and high purity.

Method for synthesis of penicillin

This invention relates to a method for synthesizing a penicillin by reacting a silylate of 6-aminopenicillanic acid and a carboxylic acid halide in the presence of an insoluble weakly basic resin having a three-dimensional structure.

Process for preparing β-lactam antibiotics

Compounds of formula (I): STR1 [in which: Z represents a group of formula STR2 R represents a hydrogen atom, a 1-pyridyl group or a group of formula --YR' (in which: R' represents an alkyl group, an alkanoyl group a carbamoyl group or a heterocyclic group; and Y represents an oxygen or a sulphur atom); X represents a hydrogen atom or a hydroxy group; and the α-amino acid moiety is in the D(-) configuration] are prepared by silylating the corresponding compound having an amino group at the 6-penam or 7-cepham position, acylating the silylated compound with D(-)-p-hydroxyphenglycyl chloride hydrochloride or D(-)-p-hydroxyphenylglycyl chloride hydrochloride and then hydrolyzing the acylated product. By carrying out the reaction in the presence of an N-alkylpyrrolidone, it is possible to improve the yields and purity of the desired product.

Process for the preparation of phosphorus derivatives of secondary ammonium salts of penam and cephem compounds

An improvement in the conversion of penam and cephem compounds to secondary ammonium salts of phosphite amides thereof by reacting as follows: STR1 wherein --R, is the non-reacting balance of the penam or cephem compound and STR2 ARE NON-REACTING SUBSTITUENTS. Catalytic amounts of H--N or the hydrogenhalide thereof may be present in the reaction medium.

Antibiotics

A new anhydrous form of ampicillin is described. The new form is stable and relatively highly soluble, and may be prepared by heating ampicillin trihydrate rapidly to a temperature of above about 100°C, for example by contact with a hot water-immiscible liquid.