Phosphorus oxychloride → 7-[2-Propoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate

HRID 1163880Notes

Reaction equation

HRID 1163880 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH2:20])[S:18][CH:19]=1)[C:12]([OH:14])=O)[CH2:7][CH3:8].C[Si](C)(C)NC(=O)C.O.O.Cl.[Cl-].[NH2:33][CH:34]1[C:51](=[O:52])[N:36]2[C:37]([C:48]([OH:50])=[O:49])=[C:38]([CH2:41][N+:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH2:39][S:40][C@H:35]12>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[CH2:6]([O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH2:20])[S:18][CH:19]=1)[C:12]([NH:33][CH:34]1[C:51](=[O:52])[N:36]2[C:37]([C:48]([O-:50])=[O:49])=[C:38]([CH2:41][N+:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:39][S:40][C@H:35]12)=[O:14])[CH2:7][CH3:8]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychloride2×HCID 25989Acetamide, N-(trimethylsilyl)-2×HCID 540960402-(2-Amino-4-thiazolyl)-2-propoxyiminoacetic acidHCID 70450238HCID 70450238, compound

Product 1

HCID 1317129257-[2-Propoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Phosphorus oxychloride (1.7 g) was added to a stirred suspension of 2-propoxyimino-2-(2-aminothiazol-4-yl)acetic acid (syn isomer) (2.0 g) in dry tetrahydrofuran (20 ml) and water (0.114 g) at 0° to 3° C. and the resulting mixture was stirred for 30 minutes and thereto was added N-trimethylsilylacetamide (1.2 g) at the same temperature. The resulting mixture was stirred for 15 minutes and thereto was added phosphorus oxychloride (1.7 g) at the same temperature and then stirred for 15 minutes. To the resulting mixture was added dry N,N-dimethylformamide (0.9 g) at the same temperature and then stirred for 30 minutes [Solution A]. N-trimethylsilylacetamide (11.4 g) was added to a stirred suspension of 1-[(7-amino-4-carboxy-3-cephem-3-yl)methyl]pyridinium chloride hydrochloride dihydrate (3.5 g) in tetrahydrofuran (70 ml). To the resulting solution was dropwise added the Solution A at -5° C. and stirred at 0° to -5° C. for 40 minutes. To the reaction mixture was added water and ethyl acetate at -5° C. The aqueous layer was separated, washed with ethyl acetate and then adjusted to pH 4.0 with 10% aqueous solution of sodium hydroxide under ice-cooling. The solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" (Trademark: Prepared by Mitsubishi Chemical Industries) and eluted with 20% aqueous solution of isopropyl alcohol. The fractions containing the object compound were collected, concentrated and lyophilized to give 7-[2-propoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (syn isomer).

Workup

  1. stirringThe resulting mixture was stirred for 15 minutes
  2. stirringstirred for 15 minutes
  3. stirringstirred at 0° to -5° C. for 40 minutes
  4. customThe aqueous layer was separated
  5. washwashed with ethyl acetate
  6. temperaturecooling
  7. customThe solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" (Trademark: Prepared by Mitsubishi Chemical Industries)
  8. washeluted with 20% aqueous solution of isopropyl alcohol
  9. additionThe fractions containing the object compound
  10. customwere collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-aec8053a0d6a4ce082a67d4b94ca769f
Source dataset
uspto-grants-1983_01
Patent number
US04367228

Reaction notes

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