Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 1656229Notes

Reaction equation

HRID 1656229 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[CH:25]=[CH:24][CH:23]=[C:22]([NH:26][CH:27]=[O:28])[N:21]=1)[C:17]([OH:19])=O)=[O:12])([CH3:9])([CH3:8])[CH3:7].[NH2:29][CH:30]1[C:55](=[O:56])[N:32]2[C:33]([C:39]([O:41][CH:42]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:40])=[C:34]([CH:37]=[CH2:38])[CH2:35][S:36][C@H:31]12.C[Si](CC(N)=O)(C)C>O1CCCC1.C(Cl)Cl.C(OCC)(=O)C.O.CN(C)C=O>[CH3:31][N+:32]([CH3:55])=[CH:33][Cl:3].[Cl-:3].[C:6]([O:10][C:11]([CH2:13][O:14][N:15]=[C:16]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([NH:26][CH:27]=[O:28])[N:21]=1)[C:17]([NH:29][CH:30]1[C:55](=[O:56])[N:32]2[C:33]([C:39]([O:41][CH:42]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[O:40])=[C:34]([CH:37]=[CH2:38])[CH2:35][S:36][C@H:31]12)=[O:19])=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

11

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12818000Benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylateHCID 536951302-(6-Formamidopyridin-2-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131713197Benzhydryl 7-[2-(6-formamidopyridin-2-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylate

Reagents, catalysts & solvents 5

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

Procedure

Vilsmeier reagent, which was prepared from N,N-dimethylformamide (0.37 ml) and phosphorus oxychloride (0.44 ml) in a conventional manner, was suspended in dried tetrahydrofuran (20 ml). 2-(tert-Butoxycarbonylmethoxyimino)-2-(6-formamidopyridin-2-yl)acetic acid (syn isomer) (3.0 g) was added thereto under ice-cooling, with stirring, and the stirring was continued at the same temperature for an hour to prepare the activated acid solution. This solution was added at a time to a solution of benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylate (2.72 g) and trimethylsilylacetamide (5.5 g) in methylene chloride at -20° C. with stirring, and the stirring was continued at -20° to -10° C. for an hour. To the reaction mixture were added water (50 ml) and ethyl acetate (200 ml), and the separated organic layer was washed with 5% aqueous sodium bicarbonate and then a saturated aqueous sodium chloride, followed by drying over magnesium sulfate. Removal of the solvent gave benzhydryl 7-[2-(tert-butoxycarbonylmethoxyimino)-2-(6-formamidopyridin-2-yl)acetamido] -3-vinyl-3-cephem-4-carboxylate (syn isomer) (4.8 g), mp 154°-157° C.

Workup

  1. temperatureunder ice-cooling
  2. waitthe stirring was continued at the same temperature for an hour
  3. customto prepare the activated acid solution
  4. stirringwith stirring
  5. waitthe stirring was continued at -20° to -10° C. for an hour
  6. washthe separated organic layer was washed with 5% aqueous sodium bicarbonate
  7. dry with materialby drying over magnesium sulfate
  8. customRemoval of the solvent

Sources & evidence

ORD record
ord-32318556b8b746c497e1b3913a9ec6a4
Source dataset
uspto-grants-1993_10
Patent number
US05252731

Reaction notes

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