Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 358084Notes

Reaction equation

HRID 358084 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:24]=[CH:23][S:22][N:21]=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](NC(=O)N[Si](C)(C)C)(C)C.Cl.[NH2:44][CH:45]1[C:66](=[O:67])[N:47]2[C:48]([C:53]([O:55][CH2:56][C:57]3[CH:62]=[CH:61][C:60]([N+:63]([O-:65])=[O:64])=[CH:59][CH:58]=3)=[O:54])=[C:49]([Cl:52])[CH2:50][S:51][C@H:46]12>C(OCC)(=O)C.O1CCCC1.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:24]=[CH:23][S:22][N:21]=1)[C:17]([NH:44][CH:45]1[C:66](=[O:67])[N:47]2[C:48]([C:53]([O:55][CH2:56][C:57]3[CH:58]=[CH:59][C:60]([N+:63]([O-:65])=[O:64])=[CH:61][CH:62]=3)=[O:54])=[C:49]([Cl:52])[CH2:50][S:51][C@H:46]12)=[O:19])=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

11

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 875621,3-Bis(trimethylsilyl)ureaHCID 539872492-Tert-butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetic acidHCID 703621504-Nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131713632p-Nitrobenzyl 7-[2-tert-butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetamido]-3-chloro-3-cephem-4-carboxylate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent was prepared from phosphorus oxychloride (1.7 g) and N,N-dimethylformamide (0.8 g) in ethyl acetate (3.2 ml) in a usual manner. 2-tert-Butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetic acid (syn isomer) (2.7 g) was added to a stirred suspension of the Vilsmeier reagent prepared above in ethyl acetate (30 ml) under ice-cooling, and the stirring was continued for 40 minutes at the same temperature to produce an activated acid solution. Bis(trimethylsilyl)urea (5.8 g) was added to a stirred suspension of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride (3.8 g) in tetrahydrofuran (40 ml), and the mixture was stirred for 20 minutes at 35° to 40° C. To this solution was added the above activated acid solution at -10° C., followed by stirring for 20 minutes at the same temperature. After water and ethyl acetate were added to the reaction mixture, the separated organic layer was washed with a saturated aqueous sodium bicarbonate and aqueous sodium chloride, and then dried over magnesium sulfate. The solution was evaporated to give p-nitrobenzyl 7-[2-tert-butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetamido]-3-chloro-3-cephem-4-carboxylate (syn isomer) (4.97 g).

Workup

  1. temperaturecooling
  2. customto produce an activated acid solution
  3. additionTo this solution was added the above activated acid solution at -10° C.
  4. stirringby stirring for 20 minutes at the same temperature
  5. washthe separated organic layer was washed with a saturated aqueous sodium bicarbonate and aqueous sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. customThe solution was evaporated

Sources & evidence

ORD record
ord-9909470d8f234b438ebd18d2db22b6ce
Source dataset
uspto-grants-1984_08
Patent number
US04464369

Reaction notes

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