Ethyl Acetate → pivaloyloxymethyl 7-[2-(Boc-L-alanyl)aminothiazol-4-yl]-2-methoxyimino-3-cephem-4-carboxylate

HRID 274242Notes

Reaction equation

HRID 274242 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]([NH:13][C@H:14]([C:16]([NH:18][C:19]1[S:20][CH:21]=[C:22]([C:24](=NOC)[C:25]([OH:27])=O)[N:23]=1)=[O:17])[CH3:15])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].NC1C(=O)[N:34]2[C:35]([C:39]([O:41][CH2:42][O:43][C:44](=[O:49])[C:45]([CH3:48])([CH3:47])[CH3:46])=[O:40])=[CH:36][CH2:37][S:38][C@H:33]12.C[Si](C)(C)[NH:54]C(=O)C.C([O:63][CH2:64]C)(=O)C>C(Cl)Cl.CN(C=O)C>[C:6]([NH:13][C@H:14]([C:16]([NH:18][C:19]1[S:20][CH:21]=[C:22]([CH:24]2[C:25](=[O:27])[N:34]3[C:35]([C:39]([O:41][CH2:42][O:43][C:44](=[O:49])[C:45]([CH3:46])([CH3:47])[CH3:48])=[O:40])=[CH:36][C:37](=[N:54][O:63][CH3:64])[S:38][C@H:33]23)[N:23]=1)=[O:17])[CH3:15])([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7]

Participants

8

Reactant 5

HCID 8857Ethyl Acetate2×HCID 24813Phosphorus oxychlorideHCID 25989Acetamide, N-(trimethylsilyl)-HCID 538373702-[2-(Boc-L-alanyl)aminothiazol-4-yl]-2-methoxyiminoacetic acidHCID 67719473Pivaloyloxymethyl 7-amino-3-cephem-4-carboxylate

Product 1

HCID 131718849pivaloyloxymethyl 7-[2-(Boc-L-alanyl)aminothiazol-4-yl]-2-methoxyimino-3-cephem-4-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

A mixture of dry ethyl acetate (1.82 ml) and dry DMF (0.36 ml) was cooled to --10° C. Phosphorus oxychloride (0.37 ml) was added thereto, and the mixture was stirred at said temperature for 20 minutes. A solution of the compound of Example 1 (1.35 g) in dry methylene chloride (8.0 ml) was added thereto, and the mixture was stirred at a temperature between -10° to -5° C. for 30 minutes. On the other hand, pivaloyloxymethyl 7-amino-3-cephem-4-carboxylate (0.95 g) was dissolved in dry methylene chloride (12 ml), and N-trimethylsilylacetamide (0.79 g) was added thereto, and the mixture was cooled to -15° C. Thereto was dropwise added the aforementioned solution, and the mixture was stirred at said temperature for 45 minutes. Ethyl acetate (200 ml) was added thereto, and the mixture was washed with 5% aqueous solution of sodium bicarbonate (100 ml) and saturated brine (100 ml). After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography eluted with benzene-ethyl acetate. The object fraction was concentrated to give 1.32 g of pivaloyloxymethyl 7-[2-(Boc-L-alanyl)aminothiazol-4-yl]-2-methoxyimino-3-cephem-4-carboxylate (synisomer).

Workup

  1. customfor 20 minutes
  2. stirringthe mixture was stirred at a temperature between -10° to -5° C. for 30 minutes
  3. temperaturethe mixture was cooled to -15° C
  4. additionThereto was dropwise added the aforementioned solution
  5. stirringthe mixture was stirred
  6. customfor 45 minutes
  7. washthe mixture was washed with 5% aqueous solution of sodium bicarbonate (100 ml) and saturated brine (100 ml)
  8. dry with materialAfter drying over anhydrous sodium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. washeluted with benzene-ethyl acetate
  11. concentrationThe object fraction was concentrated

Sources & evidence

ORD record
ord-9f5ca87869534a8cb894dd3eeb01cb1a
Source dataset
uspto-grants-1995_02
Patent number
US05389625

Reaction notes

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