Sodium Carbonate → Chloro-N,N-dimethylformiminium chloride

HRID 325973Notes

Reaction equation

HRID 325973 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH3:6][S:7][CH2:8][O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([OH:14])=O.[CH3:23][N+:24]([CH3:27])=[CH:25][Cl:26].[Cl-].O.O.Cl.[Cl-].[NH2:33][CH:34]1[C:51](=[O:52])[N:36]2[C:37]([C:48]([OH:50])=[O:49])=[C:38]([CH2:41][N+:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH2:39][S:40][C@H:35]12.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.O1CCCC1.O.CC(C)=O.CN(C)C=O>[CH3:23][N+:24]([CH3:27])=[CH:25][Cl:26].[Cl-:3].[CH3:6][S:7][CH2:8][O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([NH:33][CH:34]1[C:51](=[O:52])[N:36]2[C:37]([C:48]([O-:50])=[O:49])=[C:38]([CH2:41][N+:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:39][S:40][C@H:35]12)=[O:14]

Participants

13

Reactant 6

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 516892Sodium BicarbonateHCID 53744847HCID 53744847, compoundHCID 70450238HCID 70450238, compound

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131713490HCID 131713490, compound

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Vilsmeier reagent was prepared from phosphorus oxychloride (2.0 g) and dimethylformamide (0.95 g) in ethyl acetate (2.8 ml) in a usual manner. 2-Methylthiomethoxyimino-2-(2-formamidothiazol-4-yl) acetic acid (syn isomer) (3.0 g) was added to the stirred suspension of Vilsmeier reagent in tetrahydrofuran (30 ml) under ice cooling, and stirred for 30 minutes at the same temperature to produce an activated acid solution. On the other hand, 1-[(7-amino-4-carboxy-3-cephem-3-yl)methyl]pyridinium chloride hydrochloride dihydrate (4.0 g) was dissolved to the solution of sodium bicarbonate (2.5 g) in water (20 ml) and acetone (20 ml). To the solution was added the above activated acid solution at -3° to 3° C. and the solution was stirred for 30 minutes under keeping the pH 6.5 to 7.5 with 20% aqueous solution of sodium carbonate. Water and ethyl acetate were added to the reaction mixture and a separate aqueous layer was washed with ethyl acetate. The aqueous layer was adjusted to pH 4.5 with 10% aqueous hydrochloric acid. After removing the solvent under reduced pressuer, the aqueous solution was adjusted to pH 4.0 with 10% aqueous hydrochloric acid under ice cooling. The solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" (Trademark: prepared by Mitsubishi Chemical Industries) and eluted with 10% aqueous solution of iso-propyl alcohol. The fractions containing the object compound were concentrated and lyophilized to give 7-[2-methylthiomethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (syn isomer)(1.3 g).

Workup

  1. customto produce an activated acid solution
  2. additionTo the solution was added the above activated acid solution at -3° to 3° C.
  3. stirringthe solution was stirred for 30 minutes
  4. washa separate aqueous layer was washed with ethyl acetate
  5. customAfter removing the solvent under reduced pressuer
  6. customThe solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" (Trademark: prepared by Mitsubishi Chemical Industries)
  7. washeluted with 10% aqueous solution of iso-propyl alcohol
  8. additionThe fractions containing the object compound
  9. concentrationwere concentrated

Sources & evidence

ORD record
ord-14db42d4025a49c783c7ecca253ae496
Source dataset
uspto-grants-1984_04
Patent number
US04443444

Reaction notes

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