Water → 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-[(phenylacetyl)amino]- (2S,5R,6R)-, 4-oxide

Participants

Reaction Steps

5 ml of water and 3 g (10 mmoles) of iodobenzene dichloride in 40 ml of pyridine were added at -10° C with stirring to a suspension of 7.1 g (20 mmoles) of the sodium salt of benzylpenicillin in 160 ml of pyridine. The solution was stirred for 90 minutes and was poured into 200 ml of water and 500 ml of ethyl acetate. After adjusting the pH to 1.7 with HCl and extraction of the water layer several times with ethyl acetate, the combined organic layers were dried, concentrated and treated with diethyl ether and n-hexane. The obtained precipitate (3 g) was dissolved in water and sodium bicarbonate and the resulting solution was washed with methylene chloride, treated with decolorizing carbon, adjusted to a pH of 1.7 with HCl in the presence of methyl isobutylketone and extracted with methyl isobutylketone. The dried, concentrated organic layer was treated with diethyl ether and n-hexane and the precipitate was filtered off and dried to obtain 1.9 g of a mixture of benzylpenicillin, benzylpenicillin R-sulfoxide and benzylpenicillin-S-sulfoxide. 1.4 g of this precipitate was chromatographed on a column (65 cm in length, 2.5 cm in diameter filled with 180 g of silica gel and the eluent was a 97:3 (v/v) mixture of acetone and acetic acid. Fractions 30 to 71 contained 115 mg of the benzylpenicillin R-sulfoxide which was isolated by evaporating the solvent and dissolving the residue in ethyl acetate followed by precipitation with diethyl ether and n-hexane.

Provenance & Evidence