Cefuroxime

white crystalline solid

Broad-spectrum cephalosporin antibiotic resistant to beta-lactamase. It has been proposed for infections with gram-negative and gram-positive organisms, GONORRHEA, and HAEMOPHILUS.

Method 1: Using cefalotin sodium (I) as raw material, hydrolyze with enzyme to remove the acetyl group on the 3-position side chain, and then react with diphenylazomethane and trichloroacetyl isocyanate successively to perform the carboxyl group and alcohol Protection to obtain compound (II). Compound (II) is treated with phosphorus pentachloride to break the 7-position side chain to obtain compound (III). Compound (III) is first hydrolyzed with a weak base in methanol and then hydrolyzed with a strong acid to remove the protective group to obtain compound (IV). The compound (IV) reacts with the side chain to obtain cefuroxime. The effect of cefuroxime and sodium 2-ethylhexanoate can produce cefuroxime sodium. The preparation of the side chain and the reaction with compound (IV) can be carried out as follows. Under stirring at 0°C, 14.99g (0.072mol) of phosphorus pentachloride was suspended in 150ml of dry dichloromethane solution, and 27.5ml of N, N-dimethylformamide was added. Cool to -10°C, then add 12.17g (0.072mol) 2-(furan-2-yl)-2-methoxyiminoacetic acid (IX). After stirring and reacting at -10°C for 15 minutes, 35 g of crushed ice was added. After continuing to stir at 0*C for 10 min, separate the lower methylene chloride layer and save it for later use. 75ml N, N-dimethylformamide, 75ml acetonitrile, 42rnl triethylamine and (6R, 7R)-7-amino-3-[(carbamyloxy)methyl]cephalosporin-4- Mix the carboxylic acid, immerse it in an ice bath with stirring, and add 10 ml of water. Stir for 45 min at 0-2°C until all solids are dissolved and a yellow solution is formed. Then, within 10 minutes, add the methylene chloride solution prepared above to the yellow solution with stirring at -10°C, and the temperature will slowly rise to 0°C. Then continue the reaction at 0~2"C for 1h. Remove the cold bath and let it naturally heat up to 20"C within 1h. At 5°C, slowly add the reaction solution to a solution of 100ml of 2mol/L hydrochloric acid and 1.15L of cold water. Adjust with 2mol/L hydrochloric acid (about 10ml) to make the Ph value of the two-phase mixture Below 2, continue to stir and cool to 5°C. Precipitate out, filter, wash with 100ml of dichloromethane and 250ml of water, and dry overnight at 40°C under vacuum to obtain 22.04g of cefuroxime with a yield of 86.6%. Method 2: Using 7-aminocephalosporan acid (V) as raw material, this method is used for large-scale industrial production and is more economical. V and the required side chain are reacted in dichloromethane, and triethylamine is used as the acid binding agent, and the reaction liquid is used After washing away the alkali compounds with dilute hydrochloric acid, it is extracted with sodium bicarbonate solution, and the compound (VI) is obtained after regular treatment. Compound (VI) is fermented with yellow enzyme (yellow yesst) via Rhodidiumtoruloides (powder, can be stored at room temperature) , To remove the 3-position acetyl group. After the fermentation broth is centrifuged to remove the enzyme, acid is added to crystallize compound (VII). Starting from compound (VII), there are three ways to convert it into cefuroxime sodium. It reacts quickly with trichloroacetyl isocyanate (prepared from trichloroacetamide and oxalyl chloride) to obtain compound (VIII), and then reacts with sodium 2-ethylhexanoate in lower alcohol or glycol, cefuroxime Sodium crystallizes directly from the reaction solution. It first reacts quickly with chlorosulfonyl isocyanate (prepared from cyanogen chloride and sulfur trioxide) to obtain compound (VIII), and then reacts with sodium acetate or sodium 2-ethylhexanoate After the reaction, cefuroxime sodium is obtained. It is firstly reacted with dichlorohypophosphoryl isocyanate (prepared from methyl carbamate and phosphorus pentachloride) slowly, and the water is decomposed to obtain dihydrohypophosphoryl compound (Ⅷ), and then Heat and decompose in an aqueous solution of Ph=3.5 to obtain cefuroxime, and then react with sodium acetate or sodium 2-ethylhexanoate to obtain cefuroxime sodium.

Cephalosporin

Molecular Weight:424.4
XLogP3:-0.2
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:10
Rotatable Bond Count:8
Exact Mass:424.06888465
Monoisotopic Mass:424.06888465
Topological Polar Surface Area:199
Heavy Atom Count:29
Complexity:798
Undefined Atom Stereocenter Count:2
Undefined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes