HCID 131709947, compound → HCID 131709946, compound

HRID 1580506Notes

Reaction equation

HRID 1580506 reaction equation
[C:1]1([CH:7]([O:14][C:15]([CH:17]2[N:22]3[C:23](=[O:34])[CH:24]([C:25](=[O:33])[CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C@H:21]3[S:20][C:19]([NH2:35])=[C:18]2[CH2:36][C:37]2[CH:42]=[CH:41][C:40]([OH:43])=[C:39]([O:44][CH3:45])[CH:38]=2)=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>N1C=CC=CC=1.C(N(CC)CC)C>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:34])[C@@H:24]([C:25](=[O:33])[CH2:26][C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[C@H:21]3[S:20][CH:19]([NH2:35])[C:18]=2[CH2:36][C:37]2[CH:42]=[CH:41][C:40]([OH:43])=[C:39]([O:44][CH3:45])[CH:38]=2)=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 1

HCID 131709947HCID 131709947, compound

Product 1

HCID 131709946HCID 131709946, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8471TriethylamineSolvent

Procedure

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).

Workup

  1. custom2 days
  2. customat room temperature
  3. customevaporated to dryness several times
  4. additionwhile adding toluene
  5. customThe residue is separated by chromatography on 330 g of silica gel
  6. washelution

Sources & evidence

ORD record
ord-3ff526e87cd44eca83c907ff5674c56c
Source dataset
uspto-grants-1976_01
Patent number
US03932465

Reaction notes

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