Phosphorus oxychloride → HCID 131716061, compound

HRID 1723593Notes

Reaction equation

HRID 1723593 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]1([O:9][N:10]=[C:11]([C:15]2[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=2)[C:12]([OH:14])=O)[CH2:8][CH2:7]1.[NH2:23][C@@H:24]1[C:39](=[O:40])[N:26]2[C:27]([C:36]([OH:38])=[O:37])=[C:28]([CH2:31][O:32][C:33](=[O:35])[NH2:34])[CH2:29][S:30][C@H:25]12.C[Si](C)(C)NC(=O)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(=O)(O)[O-].[Na+]>O1CCCC1.CN(C)C=O>[CH:6]1([O:9][N:10]=[C:11]([C:15]2[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=2)[C:12]([NH:23][C@@H:24]2[C:39](=[O:40])[N:26]3[C:27]([C:36]([OH:38])=[O:37])=[C:28]([CH2:31][O:32][C:33](=[O:35])[NH2:34])[CH2:29][S:30][C@H:25]23)=[O:14])[CH2:7][CH2:8]1

Participants

9

Reactant 6

HCID 24813Phosphorus oxychlorideHCID 25989Acetamide, N-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 11391647HCID 11391647, compoundHCID 11708267BistrimethylsilylacetamidHCID 540072742-Cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetic acid

Product 1

HCID 131716061HCID 131716061, compoundYield 93.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Phosphorus oxychloride (0.53 ml) was dropwise added to N,N-dimethylformamide (0.42 ml) under ice-cooling. After stirring for 10 minutes at the same temperature, the mixture was cooled until a precipitate appeared. To the suspension was added 2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (1.12 g). The mixture was stirred at the same temperature for 30 minutes to give an activated acid solution. On the other hand, a mixture of 7β-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (1.5 g), N-trimethylsilylacetamide (1.4 g) and bis(trimethylsilyl)acetamide (2.2 g) in tetrahydrofuran (26 ml) was stirred at 30° C. for 30 minutes to give a clear solution. To the clear solution was added the activated acid solution prepared above at -30° C. The mixture was stirred for 30 minutes at -20° C. to -15° C. The mixture was poured into ice-water, adjusted to pH 7.2 with saturated aqueous solution of sodium bicarbonate, and washed with ethyl acetate. The aqueous solution was adjusted to pH 2.5 with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diisopropyl ether to give 7β-[2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (syn isomer) (2.1 g).

Workup

  1. temperaturecooling
  2. temperaturethe mixture was cooled until a precipitate
  3. stirringThe mixture was stirred at the same temperature for 30 minutes
  4. customto give an activated acid solution
  5. stirringwas stirred at 30° C. for 30 minutes
  6. customto give a clear solution
  7. additionTo the clear solution was added the activated acid solution
  8. customprepared above at -30° C
  9. stirringThe mixture was stirred for 30 minutes at -20° C. to -15° C
  10. washwashed with ethyl acetate
  11. extractionextracted with ethyl acetate
  12. washThe extract was washed with water
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated in vacuo
  15. customThe residue was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-f2c315baa2654af480a9fba1c25e9979
Source dataset
uspto-grants-1989_08
Patent number
US04861769

Reaction notes

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