Sodium Chloride → Chloro-N,N-dimethylformiminium chloride

HRID 2296008Notes

Reaction equation

HRID 2296008 reaction equation
P(Cl)(Cl)([Cl:3])=O.[C:6]([O:10][C:11]([CH2:13][O:14][N:15]=[C:16]([C:20]1[N:21]=[C:22]([NH:26][CH:27]=[O:28])[S:23][C:24]=1[Cl:25])[C:17]([OH:19])=O)=[O:12])([CH3:9])([CH3:8])[CH3:7].[CH3:29][N+:30]([CH3:33])=[CH:31][Cl:32].[Cl-].C[Si](CC(N)=O)(C)C.O.O.Cl.[Cl-].[NH2:47][CH:48]1[C:65](=[O:66])[N:50]2[C:51]([C:62]([OH:64])=[O:63])=[C:52]([CH2:55][N+:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)[CH2:53][S:54][C@H:49]12.[Cl-].[Na+].[OH-].[Na+]>C(OCC)(=O)C.O1CCCC1.CN(C)C=O>[CH3:29][N+:30]([CH3:33])=[CH:31][Cl:32].[Cl-:3].[C:6]([O:10][C:11]([CH2:13][O:14][N:15]=[C:16]([C:20]1[N:21]=[C:22]([NH:26][CH:27]=[O:28])[S:23][C:24]=1[Cl:25])[C:17]([NH:47][CH:48]1[C:65](=[O:66])[N:50]2[C:51]([C:62]([O-:64])=[O:63])=[C:52]([CH2:55][N+:56]3[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=3)[CH2:53][S:54][C@H:49]12)=[O:19])=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

12

Reactant 7

HCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 540757552-(2-Formamido-5-chlorothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acidHCID 70450238HCID 70450238, compound

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317133637-[2-t-Butoxycarbonylmethoxyimino-2-(2-formamido-5-chlorothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Vilsmeier reagent was prepared from phosphorous oxychloride (2.5 g) and N,N-dimethylformamide (1.2 g) in ethyl acetate (4.8 ml) in a usual manner. 2-(t-Butoxycarbonylmethoxyimino)-2-(2-formamido-5-chlorothiazol-4-yl)acetic acid (syn isomer) (5.0 g) was added to the stirred suspension of Vilsmeier reagent in tetrahydrofuran (70 ml) under ice-cooling, and stirred for 30 minutes at the same temperature to produce an activated acid solution. Trimethylsilylacetamide (16.4 g) was added to the stirred suspension of 1-[(7-amino-4-carboxy-3-cephem-3-yl)methyl]pyridinium chloride hydrochloride dihydrate (5.0 g) in tetrahydrofuran (100 ml). To the solution was added the above activated acid solution at -10° C. and stirred at -10° C.-5° C. for 40 minutes. A saturated aqueous sodium chloride was added to the reaction mixture and adjusted to pH 3.0 with 10% aqueous sodium hydroxide. The separated aqueous layer was extracted three times with tetrahydrofuran. The organic layer was washed with a little saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated to give 7-[2-t-butoxycarbonylmethoxyimino-2 -(2-formamido-5-chlorothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (syn isomer) (2.13 g).

Workup

  1. temperaturecooling
  2. customto produce an activated acid solution
  3. additionTo the solution was added the above activated acid solution at -10° C.
  4. stirringstirred at -10° C.-5° C. for 40 minutes
  5. extractionThe separated aqueous layer was extracted three times with tetrahydrofuran
  6. washThe organic layer was washed with a little saturated aqueous sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. customevaporated

Sources & evidence

ORD record
ord-08cca681d5ff4bdd8bd1fa5f50bdbc9e
Source dataset
uspto-grants-1984_01
Patent number
US04427677

Reaction notes

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