Dichloromethane → 3-Cephem

HRID 1155454Notes

Reaction equation

HRID 1155454 reaction equation
[N+](C1C=CC(COC(=O)/[C:11](/[N:22]2[CH:25]([S:26]S(C3C=CC(C)=CC=3)(=O)=O)[CH:24](NC(=O)COC3C=CC=CC=3)[C:23]2=[O:48])=[C:12](\OCC2C=CC=CC=2)/[CH3:13])=CC=1)([O-])=O.[N+](C1C=CC(COC(=O)/C=C\C)=CC=1)([O-])=O.N12CCCCC1C=NCCC2.C(Cl)Cl>O1CCCC1>[S:26]1[C@@H:25]2[CH2:24][C:23](=[O:48])[N:22]2[CH:11]=[CH:12][CH2:13]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 3141121,5-Diazabicyclo(5,4,0)undec-5-eneHCID 705584062-[4-(p-Toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-benzoxy-crotonic acid p-nitrobenzyl esterHCID 131711477Isocrotonic acid p-nitrobenzyl ester

Product 1

HCID 208364673-Cephem

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 731 mg (1 mmol) of a 1:1 mixture consisting of 2-[4-(p-toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-benzoxy-crotonic acid p-nitrobenzyl ester and the corresponding isocrotonic acid p-nitrobenzyl ester in a mixture of 0.185 ml (1.2 mmols) of 1,5-diazabicyclo[5.4.0]undec-5-ene in 20 ml of dry tetrahydrofurane is stirred for precisely 35 minutes at room temperature. 50 ml of methylene chloride are added to the mixture and the whole is washed successively with dilute hydrochloric acid, water and dilute aqueous sodium bicarbonate solution. The organic phase is dried over sodium sulphate and concentrated by evaporation in vacuo. The residue is chromatographed on 25 mg of acid-washed silica gel, using toluene/ethyl acetate (3:1). A mixture consisting of the ceph-2-em compound and the ceph-3-em compound in the ratio of about 3:1 is obtained; this mixture can be separated by repeated chromatography into the pure isomers, giving 7β-phenoxyacetamido-3-benzoxy-ceph-2-em-4α-carboxylic acid p-nitrobenzyl ester of melting point 160° C.-162° C. (diethyl ether/pentane); IR spectrum (methylene chloride), characteristic bands at 5.6, 5.7, 5.9 and 7.4μ, and 7β-phenoxyacetamido-3-benzoxy-ceph-3-em-4-carboxylic acid p-nitrobenzyl ester in the form of a colourless foam, IR spectrum (methylene chloride): characteristic bands at 5.6, 5.8 sh, 5.9, 7.9 and 8.4μ.

Workup

  1. washthe whole is washed successively with dilute hydrochloric acid, water and dilute aqueous sodium bicarbonate solution
  2. dry with materialThe organic phase is dried over sodium sulphate
  3. concentrationconcentrated by evaporation in vacuo
  4. customThe residue is chromatographed on 25 mg of acid-washed silica gel

Sources & evidence

ORD record
ord-bb87475ff6994d59826695460f58cdc1
Source dataset
uspto-grants-1981_11
Patent number
US04301278

Reaction notes

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