Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 569359Notes

Reaction equation

HRID 569359 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:25][CH:26]=[O:27])[S:23][CH:24]=1)[C:17]([OH:19])=O)=[O:12])([CH3:9])([CH3:8])[CH3:7].[CH3:28][N+:29]([CH3:32])=[CH:30][Cl:31].[Cl-].Cl.[NH2:35][CH:36]1[C:61](=[O:62])[N:38]2[C:39]([C:45]([O:47][CH:48]([C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[O:46])=[C:40]([CH2:43][Cl:44])[CH2:41][S:42][C@H:37]12>C(OCC)(=O)C.C[Si](CC(N)=O)(C)C.O.CN(C)C=O>[CH3:28][N+:29]([CH3:32])=[CH:30][Cl:31].[Cl-:3].[C:6]([O:10][C:11]([CH2:13][O:14][N:15]=[C:16]([C:20]1[N:21]=[C:22]([NH:25][CH:26]=[O:27])[S:23][CH:24]=1)[C:17]([NH:35][CH:36]1[C:61](=[O:62])[N:38]2[C:39]([C:45]([O:47][CH:48]([C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=3)[C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[O:46])=[C:40]([CH2:43][Cl:44])[CH2:41][S:42][C@H:37]12)=[O:19])=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

10

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 13239629Benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochlorideHCID 543909512-t-Butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131713164Benzhydryl 7-[2-tert-butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-chloromethyl-3-cephem-4-carboxylate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×HCID 357676Acetamide, 2-(trimethylsilyl)-Solvent

Procedure

Vilsmeier reagent was prepared from phosphorus oxychloride (14.8 g) and N,N-dimethylformamide (7.07 g) in ethyl acetate (50 ml) in a conventional manner. 2-(tert-Butoxycarbonylmethoxyimino)-2-(formamidothiazol-4-yl)acetic acid (syn isomer) (29 g) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (250 ml) under ice-cooling and stirred for 30 minutes at same temperature to prepare an activated acid solution. On the other hand, benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate monohydrochloride (36.1 g) was dissolved in a solution of trimethylsilylacetamide (63 g) in ethyl acetate (400 ml). To this solution was added the above activated acid solution at -12° C. and the mixture was stirred for an hour at -20° to 0° C. Water was added to the reaction mixture at 0° C. The organic layer was separated, washed with a saturated aqueous sodium bicarbonate and an aqueous sodium chloride. The solution was dried over magnesium sulfate and evaporated under reduced pressure. The residue was pulverized with diethyl ether to give benzhydryl 7-[2-tert-butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (49.7 g).

Workup

  1. temperaturecooling
  2. customto prepare an activated acid solution
  3. additionTo this solution was added the above activated acid solution at -12° C.
  4. stirringthe mixture was stirred for an hour at -20° to 0° C
  5. customThe organic layer was separated
  6. washwashed with a saturated aqueous sodium bicarbonate
  7. dry with materialThe solution was dried over magnesium sulfate
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-3a774134ef864033b4098703b423fac0
Source dataset
uspto-grants-1988_03
Patent number
US04731443

Reaction notes

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