Phosphorus oxychloride → HCID 131713537, compound

HRID 1262760Notes

Reaction equation

HRID 1262760 reaction equation
C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:21]([OH:23])=O)[N:19]=1)=[O:13].[NH2:34][CH:35]1[C:59](=[O:60])[N:37]2[C:38]([C:43]([O:45][CH:46]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)=[S:44])=[C:39]([CH3:42])[CH2:40][S:41][C@H:36]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>O1CCCC1.C(Cl)Cl.C(OCC)(=O)C.O.CN(C)C=O>[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:21]([NH:34][CH:35]2[C:59](=[O:60])[N:37]3[C:38]([C:43]([O:45][CH:46]([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)=[S:44])=[C:39]([CH3:42])[CH2:40][S:41][C@H:36]23)=[O:23])[N:19]=1)=[O:13]

Participants

12

Reactant 6

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 543909512-t-Butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetic acidHCID 131713529HCID 131713529, compound

Product 1

HCID 131713537HCID 131713537, compoundYield 67.2%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Vilsmeier reagent prepared from N,N-dimethylformamide (0.5 ml) and phosphorus oxychloride (0.58 ml) was suspended in dry tetrahydrofuran (20 ml). To a suspension was added 2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid (syn isomer, 2 g) under ice-cooling with stirring, and then the solution was stirred at the same temperature for an hour to prepare the activated acid solution. To the solution of benzhydryl 7-amino-3-methylthio-3-cephem-4-carboxylate (2.0 g) and trimethylsilylacetamide (5.0 g) in methylene chloride was added the activated acid solution obtained above all at once at -20° C., and then the mixed solution was stirred at -20° to -10° C. for an hour. Water and ethyl acetate were added to the resultant solution. The solution was adjusted to pH 7.5 with an aqueous saturated solution of sodium bicarbonate. The organic layer was washed with an aqueous saturated solution of sodium chloride, and dried over magnesium sulfate. The solvent was evaporated in vacuo to give benzhydryl 7-[2-(2-formamidothiazol- 4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-methylthio-3-cephem-4-carboxylate (syn isomer, 2.4 g). mp. 151°-157° C.

Workup

  1. temperaturecooling
  2. stirringthe solution was stirred at the same temperature for an hour
  3. customto prepare the activated acid solution
  4. customobtained above all at once at -20° C.
  5. stirringthe mixed solution was stirred at -20° to -10° C. for an hour
  6. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-02e1929bb7ce4a5e94e3d7f0c92d52cf
Source dataset
uspto-grants-1984_06
Patent number
US04452851

Reaction notes

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