HCID 131709947, compound → HCID 131709946, compound

Participants

Reaction Steps

A solution of 6.1 g of 3-(4-hydroxy-3-methoxybenzyl)-7-phenylacetyl-amino-ceph-2-em-4ξ-carboxylic acid diphenylmethyl ester in 63.5 ml of absolute pyridine and 6.5 ml of triethylamine is left to stand for 31/2 days under nitrogen at room temperature, then evaporated to dryness several times while adding toluene. The residue is separated by chromatography on 330 g of silica gel; elution is carried out with methylene chloride containing 3% methyl acetate, fractions of 250 ml each being taken. The 3-(4-hydroxy-3-methoxy-benzyl)-7β-phenylacetyl-amino-ceph-3-em-4-carboxylic acid diphenylmethyl ester is isolated in fractions 6-8, whereas fractions 9 and 10 contain a mixture of the product and the starting material. The succeeding fractions 11-16 contain principally unchaged starting material. The material from fractions 9 and 10 and the mother liquors of the crystallised products (from a mixture of methylene chloride, diethyl ether and cyclohexane) of fractions 6-8 are chromatographed once more on 130 g of silica gel. Elution is effected with methylene chloride containing 1% of ethyl acetate, fractions of 100 ml each being taken. 3-(4-Hydroxy-3-methoxy-benzyl)-7β-phenylacetyl-amino-ceph-3-em-4-carboxylic acid diphenylmethyl ester, which is almost pure according to chromatography, is eluted in fractions 6-18. These fractions are crystallised from a mixture of methylene chloride, diethyl ether and cyclohexane; the 3-(4-hydroxy-3-methoxybenzyl)-7β-phenylacetyl-amino-ceph-3-em-4-carboxylic acid diphenylmethyl ester melts at 166°-167° (the analytical sample is dried for 15 hours under a high vacuum at 35° and still contains cyclohexane according to the nuclear reasonance spectrum). The solvent can be completely removed after final drying for 20 hours at 45°; m.p. 166°-167.5°C (uncorr.) [α]D20 = -92° ± 1° (c = 0.968 in chloroform): thin-layer chromatogram (silica gel): Rf = 0.70 (system: toluene/ethyl acetate 1:1), Rf = 0.50 (system: toluene/ethyl acetate 2:1), Rf = 0.44 (system: toluene/acetone 4:1) and Rf = 0.21 (system: toluene/acetone 9:1) (the Rf values of the corresponding ceph-2-em compound are 0.68, 0.46, 0.40 and 0.15, respectively); ultraviolet absorption spectrum (in 95% ethanol): λmax = 272 mμ (ε = 9150) and λmin = 244 mμ (ε = 7300); infrared absorption spectrum: characteristic bands at: 2,78μ, 3,02μ, 5,60μ, 5,83μ, 6,02μ, 6,54μ, 6,60μ, 7,90μ, 8,08μ, 8,56μ, 8,90μ, 9,12μ and 14,41μ (in mineral oil) and 2,80μ, 2,90μ, 5,60μ, 5,78μ, 6,21μ, 6,61μ, 7,27μ, 8,12μ, 8,28μ, 8,50μ and 8,62μ (in methylene chloride).

Provenance & Evidence