Toluene ethylacetate → 3-Hydroxy-7beta-phenoxyacetylamino-cepham-4alpha-carboxylic acid diphenylmethyl ester

HRID 1155337Notes

Reaction equation

HRID 1155337 reaction equation
[C:1]1([CH:7]([O:14][C:15](=[O:51])/[C:16](/[N:24]2[CH:27]([S:28]S(C3C=CC(C)=CC=3)(=O)=O)[CH:26]([NH:39][C:40](=[O:49])[CH2:41][O:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:25]2=[O:50])=[C:17](\N2CCCC2)/[CH3:18])[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.C1(C)C=CC=CC=1.C(OCC)(=[O:61])C>C(#N)C>[C:1]1([CH:7]([O:14][C:15]([C@@H:16]2[N:24]3[C:25](=[O:50])[C@@H:26]([NH:39][C:40](=[O:49])[CH2:41][O:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[C@H:27]3[S:28][CH2:18][CH:17]2[OH:61])=[O:51])[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

Participants

4

Reactant 2

HCID 21584019Toluene ethylacetateHCID 704542582-[4-(p-Toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-(1-pyrrolidinyl)-crotonic acid diphenylmethyl ester

Product 1

HCID 705700963-Hydroxy-7beta-phenoxyacetylamino-cepham-4alpha-carboxylic acid diphenylmethyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 139.32 g (160 mmol) of a mixture consisting of the 2-[4-(p-toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-(1-pyrrolidinyl)-crotonic acid diphenylmethyl ester and the corresponding isocrotonic acid ester in 1350 ml of dry acetonitrile is heated at 80° for approximately 6 hours under nitrogen until it is no longer possible to detect any starting material by thin layer-chromatography (silica gel; toluene/ethyl acetate 1:1). The heating bath is removed, the reaction mixture containing the 7β-phenoxyacetamido-3-(1-pyrrolidinyl)-3-cephem-4-carboxylic acid diphenylmethyl ester is left to cool for a further 11/2 hours, 550 ml of 0.1 N hydrochloric acid are added and the mixture is further stirred for 81/2 hours at room temperature. The reaction mixture is diluted with ethyl acetate, the water is separated off, the organic phase is washed twice with 2 N hydrochloric acid and three times with water, dried over sodium sulphate, concentrated by evaporation in vacuo and dried under a high vacuum. The residue, containing the 7β-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylic acid diphenylmethyl ester, is used in the next step without further purification.

Workup

  1. customThe heating bath is removed
  2. additionthe reaction mixture containing the 7β-phenoxyacetamido-3-(1-pyrrolidinyl)-3-cephem-4-carboxylic acid diphenylmethyl ester
  3. waitis left
  4. temperatureto cool for a further 11/2 hours, 550 ml of 0.1 N hydrochloric acid
  5. additionare added
  6. additionThe reaction mixture is diluted with ethyl acetate
  7. customthe water is separated off
  8. washthe organic phase is washed twice with 2 N hydrochloric acid and three times with water
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated by evaporation in vacuo
  11. customdried under a high vacuum
  12. additionThe residue, containing the 7β-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylic acid diphenylmethyl ester
  13. customis used in the next step without further purification

Sources & evidence

ORD record
ord-50c0d4ac46b94510b0ba13288bfc3809
Source dataset
uspto-grants-1981_11
Patent number
US04301279

Reaction notes

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