Phosphorus oxychloride → 7-[2-(2-formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 255775Notes

Reaction equation

HRID 255775 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH2:16][O:17][CH:18]=[O:19])[C:10]([OH:12])=O)[N:8]=1)=[O:2].C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[NH2:31][CH:32]1[C:52](=[O:53])[N:34]2[C:35]([C:49]([OH:51])=[O:50])=[C:36]([CH2:39][S:40][C:41]3[N:45]([CH2:46][CH:47]=[CH2:48])[N:44]=[N:43][N:42]=3)[CH2:37][S:38][C@H:33]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH2:16][O:17][CH:18]=[O:19])[C:10]([NH:31][CH:32]2[C:52](=[O:53])[N:34]3[C:35]([C:49]([OH:51])=[O:50])=[C:36]([CH2:39][S:40][C:41]4[N:45]([CH2:46][CH:47]=[CH2:48])[N:44]=[N:43][N:42]=4)[CH2:37][S:38][C@H:33]23)=[O:12])[N:8]=1)=[O:2]

Participants

10

Reactant 6

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 541333172-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetic acidHCID 704326537-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317153037-[2-(2-formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 67.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

2-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetic acid (syn isomer, 3.6 g.) was added to Vilsmeier reagent prepared from N,N-dimethylformamide (1.1 g.) and phosphoryl chloride (2.3 g.) in dry ethyl acetate (48.4 ml.) at 0° to 5° C. and stirred for 30 minutes to give an activated acid solution. The solution was added to a solution of 7-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (4.4 g.) and trimethylsilylacetamide (11.4 g.) in ethyl acetate (88 ml.) at -10° C. and stirred at -10° to -5° C. for 1.5 hours. After adding water (100 ml.) to the resultant solution, the solution was adjusted to pH 7.0 with a saturated aqueous solution of sodium bicarbonate. The aqueous layer was separated washed with ethyl acetate and diethyl ether in turn and acidified to pH 2.5 with conc. hydrochloric acid. The precipitates were collected by filtration, washed with water and dried over phosphorus pentoxide to give 7-[2-(2-formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 5.22 g.)

Workup

  1. customto give an activated acid solution
  2. stirringstirred at -10° to -5° C. for 1.5 hours
  3. customThe aqueous layer was separated
  4. washwashed with ethyl acetate and diethyl ether in turn
  5. filtrationThe precipitates were collected by filtration
  6. washwashed with water
  7. dry with materialdried over phosphorus pentoxide

Sources & evidence

ORD record
ord-a10c28f971164f79a6f1988d5fb605f3
Source dataset
uspto-grants-1987_10
Patent number
US04698337

Reaction notes

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