Phosphorus oxychloride → HCID 131713228, compound

HRID 484816Notes

Reaction equation

HRID 484816 reaction equation
P(Cl)(Cl)(Cl)=O.[S:6]1[CH2:9][CH:8]([O:10][N:11]=[C:12]([C:16]2[N:17]=[C:18]([NH:21][CH:22]=[O:23])[S:19][CH:20]=2)[C:13]([OH:15])=O)[CH2:7]1.C[Si](CC(N)=O)(C)C.Cl.[Cl-].[NH2:34][CH:35]1[C:52](=[O:53])[N:37]2[C:38]([C:49]([OH: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>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[S:6]1[CH2:7][CH:8]([O:10][N:11]=[C:12]([C:16]2[N:17]=[C:18]([NH:21][CH:22]=[O:23])[S:19][CH:20]=2)[C:13]([NH:34][CH:35]2[C:52](=[O:53])[N:37]3[C:38]([C:49]([O-:51])=[O:50])=[C:39]([CH2:42][N+:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[CH2:40][S:41][C@H:36]23)=[O:15])[CH2:9]1

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 53855623HCID 53855623, compoundHCID 70354029HCID 70354029, compound

Product 1

HCID 131713228HCID 131713228, compoundYield 41%

Reagents, catalysts & solvents 4

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

Procedure

Vilsmeir reagent was prepared from N,N-dimethylformamide (0.52 g) and phosphorus oxychloride (1.1 g) in a usual manner. 2-(3-Thietanyloxyimino)-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (1.5 g) was added to the stirred suspension of Vilsmeir reagent in tetrahydrofuran (15 ml) under ice-cooling and the mixture was stirred for 30 minutes at below 5° C. The mixture became clear solution [Solution A]. A mixture of trimethylsilylacetamide (7.2 g) and 1-[(7-amino-4-carboxy-3-cephem-3-yl)methyl]pyridinium chloride hydrochloride (2.0 g) in tetrahydrofuran (40 ml) was stirred at 45° C. for 30 minutes. To the mixture was added the above Solution A all at once at -30° C., and the resulting solution was stirred at -15° C. for 30 minutes. Water (50 ml) and ethyl acetate (50 ml) were added to the reaction mixture at -10° C. The organic layer was separated and the aqueous layer was extracted twice with a mixture of ethyl acetate (50 ml) and tetrahydrofuran (50 ml). The combined organic layers were dried over magnesium sulfate and evaporated in vacuo. The residue was pulverized with diisopropyl ether to give 7-[2-(3-thietanyloxyimino)-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (syn isomer) (1.2 g).

Workup

  1. temperaturecooling
  2. stirringwas stirred at 45° C. for 30 minutes
  3. stirringthe resulting solution was stirred at -15° C. for 30 minutes
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted twice with a mixture of ethyl acetate (50 ml) and tetrahydrofuran (50 ml)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-f696bd578f7f4cd58ff4c0f374e1288f
Source dataset
uspto-grants-1985_08
Patent number
US04533738

Reaction notes

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