Diisopropyl Ether → HCID 131714498, compound

HRID 1284592Notes

Reaction equation

HRID 1284592 reaction equation
[CH2:1]([O:3][N:4]=[C:5]([C:9]1[N:13]=[C:12]([NH:14][P:15]([NH2:18])([NH2:17])=[O:16])[S:11][N:10]=1)[C:6]([O-:8])=O)[CH3:2].[Na+].C(=O)(O)[O-].[Na+].CS(Cl)(=O)=O.O.O.Cl.Cl.[NH2:34][CH:35]1[C:52](=[O:53])[N:37]2[C:38]([C:49]([O-:51])=[O:50])=[C:39]([CH2:42][N+:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:40][S:41][C@H:36]12.C(OC(C)C)(C)C>CN(C)C(=O)C.C(Cl)Cl>[CH2:1]([O:3][N:4]=[C:5]([C:9]1[N:13]=[C:12]([NH:14][P:15]([NH2:18])([NH2:17])=[O:16])[S:11][N:10]=1)[C:6]([NH:34][CH:35]1[C:52](=[O:53])[N:37]2[C:38]([C:49]([O-:51])=[O:50])=[C:39]([CH2:42][N+:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH2:40][S:41][C@H:36]12)=[O:8])[CH3:2]

Participants

8

Reactant 5

HCID 7914Diisopropyl EtherHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 67897133HCID 67897133, compoundHCID 74088771HCID 74088771, compound

Product 1

HCID 131714498HCID 131714498, compoundYield 32.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-20 °C

Procedure

To a mixture of sodium 2-ethoxyimino-2-(5-diaminophosphorylamino-1,2,4-thiadiazol-3-yl)acetate (syn isomer) (2.10 g) and sodium bicarbonate (1.12 g) in N,N-dimethylacetamide (21 ml) was added methanesulfonyl chloride (1.03 ml) under cooling in an ice-bath and stirring, which was continued for one hour and 45 minutes and cooled to -20° C. To the cold reaction mixture was added a solution of 7-amino-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate dihydrochloride dihydrate (2.39 g) and monotrimethylsilylacetamide (11.96 g) in methylene chloride (48 ml) at -18° C. under stirring, which was continued for 30 minutes at -18° to -12° C. and for 30 minutes at -10° to 0° C. The reaction mixture was poured into diisopropyl ether (700 ml) and the resulting precipitates were separated by decantation. The residue was dissolved in water (100 ml), adjusted to pH 3.8 with 1N hydrochloric acid and subjected to column chromatography on a non-ionic adsorption resin "Diaion HP-20" (105 ml). After the column was washed with water (500 ml), the elution was carried out with 20% aqueous methanol. The fractions containing the object compound were collected, evaporated to remove methanol and lyophilized to give 7-[2-ethoxyimino-2-(5-diaminophosphorylamino-1,2,4-thiadiazol-3-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (syn isomer) (1.11 g), mp 123° to 132° C. (dec.).

Workup

  1. temperatureunder cooling in an ice-bath
  2. customTo the cold reaction mixture
  3. stirringunder stirring
  4. waitwhich was continued for 30 minutes at -18° to -12° C. and for 30 minutes at -10° to 0° C
  5. customthe resulting precipitates
  6. customwere separated by decantation
  7. dissolutionThe residue was dissolved in water (100 ml)
  8. washAfter the column was washed with water (500 ml)
  9. washthe elution
  10. additionThe fractions containing the object compound
  11. customwere collected
  12. customevaporated
  13. customto remove methanol

Sources & evidence

ORD record
ord-da5a7ce54ebb450a8b117987d8462ed8
Source dataset
uspto-grants-1986_01
Patent number
US04563449

Reaction notes

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