Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 2351135Notes

Reaction equation

HRID 2351135 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH3:20])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[CH3:21][N+:22]([CH3:25])=[CH:23][Cl:24].[Cl-].[NH2:27][CH:28]1[C:60](=[O:61])[N:30]2[C:31]([C:44]([O:46][CH:47]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:45])=[C:32]([S:35]/[CH:36]=[CH:37]\[C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[CH2:33][S:34][C@H:29]12.C[Si](NC(=O)N[Si](C)(C)C)(C)C>C(OCC)(=O)C.O1CCCC1.O.CN(C)C=O>[CH3:21][N+:22]([CH3:25])=[CH:23][Cl:24].[Cl-:3].[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH3:20])[C:15]([NH:27][CH:28]2[C:60](=[O:61])[N:30]3[C:31]([C:44]([O:46][CH:47]([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)=[O:45])=[C:32]([S:35]/[CH:36]=[CH:37]\[C:38]4[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=4)[CH2:33][S:34][C@H:29]23)=[O:17])[N:13]=1)=[O:7]

Participants

11

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 875621,3-Bis(trimethylsilyl)ureaHCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 67948113benzhydryl 7-amino-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131716149benzhydryl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Vilsmeier reagent was prepared from N,N-dimethylformamide (1.26 g) and phosphorus oxychloride (2.64 g) in ethyl acetate (26.5 ml) in a usual manner. 2-(2-Formamidothiazol-4-yl) -2-methoxyiminoacetic acid (syn isomer) (3.29 g) was added to the stirred suspension of Vilsmeier reagent under ice-cooling and the mixture was stirred for 30 minutes at the same temperature to give an activated acid solution. To a solution of benzhydryl 7-amino-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate (6 g) and bis(trimethylsilyl)urea (9.78 g) in tetrahydrofuran (60 ml) was added the activated solution obtained above at -30°, and the mixture was stirred at -20° to -10° C. for 30 minutes. Water and ethyl acetate were added to the resultant solution under stirring and the separated organic layer was washed with a saturated aqueous solution of sodium bicarbonate and brine, dried over magnesium sulfate. The organic solution was evaporated in vacuo to give a residue. The residue was subjected to column chromatography on silica gel and eluted with a mixture of ethyl acetate and methylene chloride (1:1). The fractions containing the object compound were combined and evaporated in vacuo to give benzhydryl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate (syn isomer) (3.09 g).

Workup

  1. temperaturecooling
  2. customto give an activated acid solution
  3. customobtained above at -30°
  4. stirringthe mixture was stirred at -20° to -10° C. for 30 minutes
  5. stirringunder stirring
  6. washthe separated organic layer was washed with a saturated aqueous solution of sodium bicarbonate and brine
  7. dry with materialdried over magnesium sulfate
  8. customThe organic solution was evaporated in vacuo
  9. customto give a residue
  10. washeluted with a mixture of ethyl acetate and methylene chloride (1:1)
  11. additionThe fractions containing the object compound
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-04285bf66e5b4a1493a99b407bac6f63
Source dataset
uspto-grants-1989_10
Patent number
US04871730

Reaction notes

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