Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 980986Notes

Reaction equation

HRID 980986 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-].C[Si](C)(C)NC(=O)C.[NH2:35][CH:36]1[C:67](=[O:68])[N:38]2[C:39]([C:51]([O:53][CH:54]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[O:52])=[C:40]([CH:43]=[CH:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][N:46]=3)[CH2:41][S:42][C@H:37]12>C(OCC)(=O)C.O1CCCC1.O>[CH3:21][N+:22]([CH3:25])=[CH:23][Cl:24].[Cl-:3].[CH3:20][O:19][N:18]=[C:14]([C:12]1[N:13]=[C:9]([NH:8][CH:6]=[O:7])[S:10][CH:11]=1)[C:15]([NH:35][CH:36]1[C:67](=[O:68])[N:38]2[C:39]([C:51]([O:53][CH:54]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[C:55]3[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=3)=[O:52])=[C:40]([CH:43]=[CH:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][N:46]=3)[CH2:41][S:42][C@H:37]12)=[O:17]

Participants

10

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 25989Acetamide, N-(trimethylsilyl)-HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 131714364Benzhydryl 7-amino-3-[2-(2-pyridyl)vinyl]-3-cephem-4-carboxylate

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131714365Benzhydryl 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-[2-(2-pyridyl)vinyl]-3-cephem-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent was prepared from phosphorus oxychloride (1.29 g) and dimethylformamido (0.62 g) in ethyl acetate (30 ml) in a usual manner. 2-(2-Formamidothiazol-4-yl)-2-methoxyiminoacetic acid (syn isomer) (1.6 g) was added to the stirred suspension of the Vilsmeier reagent in ethyl acetate (2 ml) and tetrahydrofuran (10 ml) under ice-cooling and stirred at the same temperature for 0.5 hours to produce an activated acid solution. N-(Trimethylsilyl)acetamide (5.0 g) was added to the stirred suspension of benzhydryl 7-amino-3-[2-(2-pyridyl)vinyl]-3-cephem-4-carboxylate (trans isomer) (3 g) in ethyl acetate (30 ml) and stirred at 40° to 43° C. for 30 minutes. To the clear solution was added the activated acid solution prepared above at -20° C. and stirred at the same temperature for 30 minutes. Water (30 ml) was added to the resulting solution, and separated organic layer was washed with 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate and evaporated to give benzhydryl 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-[2-(2-pyridyl)vinyl]-3-cephem-4-carboxylate (syn isomer) (trans isomer) (4.1 g).

Workup

  1. temperaturecooling
  2. customto produce an activated acid solution
  3. stirringstirred at 40° to 43° C. for 30 minutes
  4. additionTo the clear solution was added the activated acid solution
  5. customprepared above at -20° C.
  6. stirringstirred at the same temperature for 30 minutes
  7. customseparated organic layer
  8. washwas washed with 5% aqueous sodium bicarbonate and brine
  9. dry with materialdried over magnesium sulfate
  10. customevaporated

Sources & evidence

ORD record
ord-ce4ac9887488408dbf5cf8c21f5b0f67
Source dataset
uspto-grants-1987_01
Patent number
US04639448

Reaction notes

Loading…