Diethyl Ether → 7beta-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetamido]-3-[3-acetamido-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate

HRID 1376419Notes

Reaction equation

HRID 1376419 reaction equation
[NH2:1][C@@H:2]1[C:28](=[O:29])[N:4]2[C:5]([C:25]([O-:27])=[O:26])=[C:6]([CH2:9][N+:10]3[N:11]([CH2:19][CH2:20][O:21]C(=O)C)[C:12]([NH:15][C:16](=[O:18])[CH3:17])=[CH:13][CH:14]=3)[CH2:7][S:8][C@H:3]12.C[Si](C)(C)NC(=O)C.Cl.[NH2:39][C:40]1[S:44][N:43]=[C:42](/[C:45](=[N:49]/[O:50][CH2:51][CH:52]=[CH2:53])/[C:46](Cl)=[O:47])[N:41]=1.CCOCC>ClCCl>[NH2:39][C:40]1[S:44][N:43]=[C:42]([C:45](=[N:49][O:50][CH2:51][CH:52]=[CH2:53])[C:46]([NH:1][C@@H:2]2[C:28](=[O:29])[N:4]3[C:5]([C:25]([O-:27])=[O:26])=[C:6]([CH2:9][N+:10]4[N:11]([CH2:19][CH2:20][OH:21])[C:12]([NH:15][C:16](=[O:18])[CH3:17])=[CH:13][CH:14]=4)[CH2:7][S:8][C@H:3]23)=[O:47])[N:41]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 25989Acetamide, N-(trimethylsilyl)-HCID 20075415(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-prop-2-enoxyiminoacetyl chloride;hydrochlorideHCID 1317201417beta-Amino-3-[3-acetamido-2-(2-acetoxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate

Product 1

HCID 1317201397beta-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetamido]-3-[3-acetamido-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylateYield 20.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of di(trifluoroacetic acid) salt of 7β-amino-3-[3-acetamido-2-(2-acetoxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate (1 g) and N-(trimethylsilyl)acetamide (2.01 g) in dichloromethane (20 ml) was added (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetyl chloride hydrochloride (0.520 g) under stirring and ice-cooling. The mixture was stirred for one hour at room temperature. The reaction mixture was added to ether under stirring and ice-cooling. The produced amorphous solid was dried in vacuo and dissolved in water. The aqueous solution was adjusted to pH 13 with 1N aqueous sodium hydroxide under stirring at -3°~0° C. and stirred for 2 hours at the same temperature. The aqueous solution was adjusted to pH 2 with 1N hydrochloric acid and subjected to column chromatography on Diaion HP-20 and the elution was carried out with 10% aqueous isopropyl alcohol. The fractions containing the object compound were combined, concentrated to remove isopropyl alcohol and lyophilized to give 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetamido]-3-[3-acetamido-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate (syn isomer) (222 mg).

Workup

  1. temperatureice-cooling
  2. stirringThe mixture was stirred for one hour at room temperature
  3. stirringunder stirring
  4. temperatureice-cooling
  5. customThe produced amorphous solid was dried in vacuo
  6. dissolutiondissolved in water
  7. stirringunder stirring at -3°~0° C.
  8. stirringstirred for 2 hours at the same temperature
  9. washthe elution
  10. additionThe fractions containing the object compound
  11. concentrationconcentrated
  12. customto remove isopropyl alcohol

Sources & evidence

ORD record
ord-5c718f78f9b641d19c99017ae9dfd653
Source dataset
uspto-grants-1997_09
Patent number
US05663163

Reaction notes

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