Acetic Acid → 3-Hydroxy-7beta-phenoxyacetylamino-3-cephem-4-carboxylic acid diphenylmethyl ester

HRID 1155437Notes

Reaction equation

HRID 1155437 reaction equation
C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[C:13]1([CH:19]([O:26][C:27](=[O:59])/[C:28](/[N:32]2[CH:35]([S:36]S(C3C=CC(C)=CC=3)(=O)=O)[CH:34]([NH:47][C:48](=[O:57])[CH2:49][O:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[C:33]2=[O:58])=[C:29](\[OH:31])/[CH3:30])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N12CCCCC1C=NCCC2.C(O)(=O)C>COCCOC.C(Cl)Cl>[C:13]1([CH:19]([O:26][C:27]([C:28]2[N:32]3[C:33](=[O:58])[C@@H:34]([NH:47][C:48](=[O:57])[CH2:49][O:50][C:51]4[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=4)[C@H:35]3[S:36][CH2:30][C:29]=2[OH:31])=[O:59])[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3141121,5-Diazabicyclo(5,4,0)undec-5-eneHCID 11708267BistrimethylsilylacetamidHCID 70454173HCID 70454173, compound

Product 1

HCID 547082513-Hydroxy-7beta-phenoxyacetylamino-3-cephem-4-carboxylic acid diphenylmethyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

0.12 ml of bis-trimethylsilyl-acetamide (0.508 mmol) is added to a solution of 301 mg (0.462 mmol) of 2-[4-(p-toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-hydroxy-crotonic acid diphenylmethyl ester in 3 ml of 1,2-dimethoxyethane under a nitrogen atmosphere, and the mixture is stirred for one hour at room temperature. The solution is completely concentrated by evaporation and the oily residue is dried for one hour under a high vacuum. The silylated crude product is taken up in 3 ml of dried 1,2-diethoxyethane and after cooling to 0° C. 0.075 ml (0.508 mmol) of 1,5-diazabicyclo [5.4.0]undec-5-ene is added. After 6 hours' reaction time at 0° C. under a nitrogen atmosphere, 0.3 ml of acetic acid is added and the mixture is diluted with methylene chloride. The methylene chloride solution is washed successively with dilute sulphuric acid, water and dilute bicarbonate solution. The aqueous phases are extracted with methylene chloride and the combined organic phases are dried with sodium sulphate, concentrated in vacuo and dried under a high vacuum. Crude 7β-phenoxyacetamido-3-hydroxy-ceph-3-em-4-carboxylic acid diphenylmethyl ester is obtained. An excess of a solution of diazomethane in ether is added to the solution of the crude product in chloroform at 0° C. and the mixture is left to stand for 5 minutes at 0° C. It is then concentrated completely and the residue is chromatographed on silica gel, as in Example 2. 7β-Phenoxyacetamido-3-methoxy-ceph-3-em-4-carboxylic acid diphenylmethyl ester; Rf value=0.19 (silica gel; toluene/ethyl acetate, 3:1); melting point 120° C. (from ether), IR spectrum (in CHCl3); 3,310, 1,775, 1,710, 1,690 and 1,600 cm-1, is obtained.

Workup

  1. concentrationThe solution is completely concentrated by evaporation
  2. customthe oily residue is dried for one hour under a high vacuum
  3. temperatureafter cooling to 0° C
  4. customAfter 6 hours' reaction time at 0° C. under a nitrogen atmosphere
  5. washThe methylene chloride solution is washed successively with dilute sulphuric acid, water and dilute bicarbonate solution
  6. extractionThe aqueous phases are extracted with methylene chloride
  7. dry with materialthe combined organic phases are dried with sodium sulphate
  8. concentrationconcentrated in vacuo
  9. customdried under a high vacuum

Sources & evidence

ORD record
ord-e92189ba78ef4e3cbc21377a6eb8c11d
Source dataset
uspto-grants-1981_11
Patent number
US04301278

Reaction notes

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