Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 615412Notes

Reaction equation

HRID 615412 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]=[CH:22][S:23][CH:24]=1)[C:17]([OH:19])=O)=[O:12])([CH3:9])([CH3:8])[CH3:7].[CH3:25][N+:26]([CH3:29])=[CH:27][Cl:28].[Cl-].C[Si](CC(N)=O)(C)C.[NH2:39][CH:40]1[C:65](=[O:66])[N:42]2[C:43]([C:49]([O:51][CH:52]([C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)[C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)=[O:50])=[C:44]([CH2:47][Cl:48])[CH2:45][S:46][C@H:41]12>C(OCC)(=O)C.O.CN(C)C=O>[CH3:25][N+:26]([CH3:29])=[CH:27][Cl:28].[Cl-:3].[C:6]([O:10][C:11]([CH2:13][O:14][N:15]=[C:16]([C:20]1[N:21]=[CH:22][S:23][CH:24]=1)[C:17]([NH:39][CH:40]1[C:65](=[O:66])[N:42]2[C:43]([C:49]([O:51][CH:52]([C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=3)[C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)=[O:50])=[C:44]([CH2:47][Cl:48])[CH2:45][S:46][C@H:41]12)=[O:19])=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

10

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 13239626Benzhydryl 7-Amino-3-chloromethyl-3-cephem-4-carboxylateHCID 54472737HCID 54472737, compound

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131714103Benzhydryl 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-chloromethyl-3-cephem-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent was prepared from phosphorus oxychloride (14.4 g) and N,N-dimethylformamide (6.9 g) in ethyl acetate (27.6 ml) in a usual manner. 2-t-Butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetic acid (syn isomer) (22.8 g) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (200 ml) under ice-cooling and the mixture was stirred for 20 minutes at the same temperature to produce an activated acid solution. Trimethylsilylacetamide (56.9 g) was added to a stirred suspension of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate (30 g) in ethyl acetate (300 ml) and the resultant mixture was stirred for 30 minutes at ambient temperature. To the solution was added the activated acid solution obtained above at -10° C. and the mixture was stirred for 30 minutes at the same temperature. Water was added to the reaction mixture, and the separated organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, successively. The ethyl acetate layer was dried over magnesium sulfate and evaporated to give benzhydryl 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (37.3 g).

Workup

  1. temperaturecooling
  2. customto produce an activated acid solution
  3. additionTo the solution was added the activated acid solution
  4. customobtained above at -10° C.
  5. stirringthe mixture was stirred for 30 minutes at the same temperature
  6. washthe separated organic layer was washed with a saturated aqueous solution of sodium bicarbonate
  7. dry with materialThe ethyl acetate layer was dried over magnesium sulfate
  8. customevaporated

Sources & evidence

ORD record
ord-6a87edf9da864810a31c086466d28ccf
Source dataset
uspto-grants-1985_02
Patent number
US04499088

Reaction notes

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