Phosphorus oxychloride → 7-[2-methoxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

HRID 904874Notes

Reaction equation

HRID 904874 reaction equation
[CH3:1][O:2][N:3]=[C:4]([C:8]1[N:9]=[C:10]([NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[S:11][CH:12]=1)[C:5]([OH:7])=O.C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[NH2:31][CH:32]1[C:57](=[O:58])[N:34]2[C:35]([C:54]([OH:56])=[O:55])=[C:36]([CH2:39][S:40][C:41]3[N:45]([CH2:46][C:47]([C:51]([OH:53])=[O:52])=[N:48][O:49][CH3:50])[N:44]=[N:43][N:42]=3)[CH2:37][S:38][C@H:33]12.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O1CCCC1.O.CC(C)=O.CN(C)C=O>[CH3:1][O:2][N:3]=[C:4]([C:8]1[N:9]=[C:10]([NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[S:11][CH:12]=1)[C:5]([NH:31][CH:32]1[C:57](=[O:58])[N:34]2[C:35]([C:54]([OH:56])=[O:55])=[C:36]([CH2:39][S:40][C:41]3[N:45]([CH2:46][C:47]([C:51]([OH:53])=[O:52])=[N:48][O:49][CH3:50])[N:44]=[N:43][N:42]=3)[CH2:37][S:38][C@H:33]12)=[O:7]

Participants

11

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 516892Sodium BicarbonateHCID 540662192-Methoxyimino-2-(2-trifluoroacetylaminothiazol-4-yl)acetic acidHCID 1317132437-amino 3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317132447-[2-methoxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 5

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

Procedure

2-Methoxyimino-2-[2-(2,2,2-trifluoroacetamido)thiazol-4-yl]acetic acid (syn isomer) (0.97 g) was added at 0° C. to vilsmeier reagent which had been prepared from N,N-dimethylformamide (0.31 g) and phosphoryl chloride (0.65 g) in ethyl acetate (1.2 ml) and tetrahydrofuran (7.4 ml), and the mixture was stirred at the same temperature for 30 minutes to afford the activated solution. The activated solution was added dropwise at -5 to 0 C. to a solution of 7-amino-3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (1.40 g) in water (10 ml) and acetone (8 ml), adjusted to pH 8.0 with sodium bicarbonate and the mixture was stirred at the same temperature for 45 minutes. To the resultant mixture was added ethyl acetate (10 ml), and the aqueous phase was separated from the mixture. To the aqueous solution was added ethyl acetate (70 ml) and the mixture was adjusted to pH 2.0 with 10% hydrochloric acid with stirring, and the ethyl acetate layer was separated, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated. The residue was pulverized with diisopropyl ether to give 7-[2-methoxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-[1-(2-carboxy-2-methoxyiminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer: in the 7-position) (1.77 g), mp 164° to 170° C. (dec.).

Workup

  1. customto afford the activated solution
  2. additionThe activated solution was added dropwise at -5 to 0 C
  3. stirringthe mixture was stirred at the same temperature for 45 minutes
  4. customthe aqueous phase was separated from the mixture
  5. additionTo the aqueous solution was added ethyl acetate (70 ml)
  6. stirringwith stirring
  7. customthe ethyl acetate layer was separated
  8. washwashed with a saturated aqueous solution of sodium chloride
  9. dry with materialdried over magnesium sulfate
  10. customevaporated

Sources & evidence

ORD record
ord-10a1d379c17c4493bbb1b9aad46e1523
Source dataset
uspto-grants-1983_12
Patent number
US04420477

Reaction notes

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