21649-57-0

Usage

Originator

Carfecillin sodium ,Beecham (GSK)

Uses

Antibacterial.

Manufacturing Process

Phenylmalonic acid (27 g) was mixed with dry ether (80 ml) and treated with thionyl chloride (17.85 g, 10.9 ml) and dimethylformamide (4 drops). The mixture was refluxed for 3 hours on a hot water bath. The solvent was evaporated under reduced pressure and the residue dissolved in fresh dry ether (80 ml). Phenol (14.1 g) was added all at once and the mixture refluxed for 2 hours. The reaction was cooled to room temperature, washed with water (25 ml) and extracted with saturated sodium bicarbonate solution until the extracts were alkaline. The combined aqueous extracts were washed with ether (100 ml) and acidified with 5 N HCl. The precipitated oil was extracted with methylene chloride. The combined organic extracts were washed thoroughly with water (6x120 ml) dried over anhydrous magnesium sulphate and evaporated. The solid residue was crystallised from benzene to give monophenyl phenylmalonate, a colourless crystalline solid 30.2 g (78.7 %) MP 115-117°C. This product (5.12 g, 0.02 m) was mixed with thionyl chloride (20 ml) and heated in a water bath at 75°C for 1 hour. The excess thionyl chloride was evaporated under reduced pressure. The residue was mixed with dry benzene (10 ml) and again evaporated to dryness to remove residual thionyl chloride. The final residue was dissolved in dry acetone (100 ml) and added, with stirring, to a solution of 6-aminophenicillanic acid (4.32) in water (100 ml), 1 N sodium hydroxide (20 ml), 1 N sodium bicarbonate solution (30 ml) and acetone (50 ml) cooled to 12°C. The reaction mixture was stirred for 2 hours. The resulting mixture was stirred at room temperature for 2 hours. The resulting solution was extracted with ether (3x60 ml) and the extracts discarded. The aqueous layer was covered with ether (60 ml) and acidified with 1 N HCl to pH 2. The ether layer was separated and the aqueous layer extracted with ether (2x60 ml). The combine ether extracts were washed with water (20 ml) and extracted with 1 N sodium bicarbonate solution to pH 7. The neutral aqueous extract was evaporated under reduced temperature and pressure. The residue was dried over phosphorous pentoxide in vacuo to give 6.7 (70.4%) of penicillin salt as an amorphous solid. The solid, when dissolved in ethanol (50 ml) at room temperature gave on standing 30 min the penicillin salt as a colorless crystalline solid 5.23 g (78.1 %).

Therapeutic Function

Antibiotic

InChI:InChI=1/C23H22N2O6S.Na/c1-23(2)17(21(28)29)25-19(27)16(20(25)32-23)24-18(26)15(13-9-5-3-6-10-13)22(30)31-14-11-7-4-8-12-14;/h3-12,15-17,20H,1-2H3,(H,24,26)(H,28,29);/q;+1/p-1/t15?,16-,17+,20-;/m1./s1

Relevant academic research and scientific papers

Nuclear Magnetic Resonance and Circular Dichroism of Penicillins derived from Disubstituted Acetic Acids

N.m.r. and c.d. spectra of some isomeric pairs of penicillins derived from disubstituted acetic acids are reported.For those penicillins which have an aromatic group attached to C-10 empirical correlations are observed between the configuration at C-10 and, (a) the sign of a c.d. band at 200-210 nm, and (b) the chemical shift of the 3-H and methyl protons.These correlations are used to assign the R configuration to the crystalline methyl (3) and ethyl (4) esters of carbenicillin and to the calcium insoluble isomers of carbenicillin (8) and ticarcillin (9).Many of the penicillins show an upfield shift of the metyhl protons relative to their position in 6-aminopenicillanic acid (16).This is ascribed to shielding effects of the side-chain aromatic ring produced by folded conformations of the side-chain.For the penicillins (14) and (15) derived from tyrosine, side-chain rotamer proportions calculated from coupling constants are discussed in relation to chemical shifts.Bands at about 230 and 260 -280 nm in the c. d. spectra are discussed in comparison with previous c. d. studies of penicillins and the relevant side-chain acids.