3-((Acetyloxy)methyl)-7-amino-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid → HCID 20499081, compound

HRID 2166745Notes

Reaction equation

HRID 2166745 reaction equation
[C:1]([O:4][CH2:5][C:6]1[CH2:13][S:12][CH:11]2[N:8]([C:9](=[O:15])[CH:10]2[NH2:14])[C:7]=1[C:16]([OH:18])=[O:17])(=[O:3])[CH3:2].[NH2:19][C:20]([CH:30]([F:32])[F:31])([CH2:24][C:25]1[NH:29][CH:28]=[N:27][CH:26]=1)[C:21](Cl)=[O:22]>C(OCC)(=O)C>[NH2:19][C:20]([CH:30]([F:32])[F:31])([CH2:24][C:25]1[NH:29][CH:28]=[N:27][CH:26]=1)[C:21]([NH:14][CH:10]1[C:9](=[O:15])[N:8]2[CH:11]1[S:12][CH2:13][C:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])=[C:7]2[C:16]([OH:18])=[O:17])=[O:22]

Participants

4

Reactant 2

HCID 137293-((Acetyloxy)methyl)-7-amino-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidHCID 54222001HCID 54222001, compound

Product 1

HCID 20499081HCID 20499081, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1 g of 3-acetyloxymethyl-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid and 1 g of 2-amino-2-difluoromethyl-3-(5-imidazolyl)propionic acid chloride wherein the free amino groups are protected with tertiary-butoxycarbonyl in 50 ml of ethyl acetate is refluxed for 2 hours after which the solvent is removed leaving a residue which is chromatographed on silica gel using benzene-acetone as the eluant to give 7-[[2-amino-2-difluoromethyl-3-(5-imidazolyl)propionyl]amino]-3-acetoxymethyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid wherein the amino groups are protected with tert-butoxycarbonyl. The protected cephalosporin compound is treated with trifluoroacetic acid for 1/2 hour at 25° C. under nitrogen atmosphere then diluted with ether until precipitation stops and filtered to give the di-trifluoroacetic acid salt of the title cephalosporin which can be converted to free base by use of ion exchange resin.

Workup

  1. temperatureis refluxed for 2 hours after which the solvent
  2. customis removed
  3. customleaving a residue which
  4. customis chromatographed on silica gel

Sources & evidence

ORD record
ord-11c8ebf5c9734e9da1efeac8bc51954c
Source dataset
uspto-grants-1983_06
Patent number
US04388466

Reaction notes

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