Phosphorus oxychloride → 7-[2-{2-(2,2,2-Trifluoroacetamido)-4-thiazolyl}--methoxyiminoacetamido]-3-methoxy-3-cephem-4-carboxylic acid

HRID 364508Notes

Reaction equation

HRID 364508 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]([NH:5][C:6]1[S:7][CH:8]=[C:9]([C:11](=[N:15][O:16][CH3:17])[C:12]([OH:14])=O)[N:10]=1)=[O:4].P(Cl)(Cl)(Cl)=O.Cl.[NH2:26][CH:27]1[C:39](=[O:40])[N:29]2[C:30]([C:36]([OH:38])=[O:37])=[C:31]([O:34][CH3:35])[CH2:32][S:33][C@H:28]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[F:18][C:2]([F:1])([F:19])[C:3]([NH:5][C:6]1[S:7][CH:8]=[C:9]([C:11](=[N:15][O:16][CH3:17])[C:12]([NH:26][CH:27]2[C:39](=[O:40])[N:29]3[C:30]([C:36]([OH:38])=[O:37])=[C:31]([O:34][CH3:35])[CH2:32][S:33][C@H:28]23)=[O:14])[N:10]=1)=[O:4]

Participants

8

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 540662192-Methoxyimino-2-(2-trifluoroacetylaminothiazol-4-yl)acetic acidHCID 703620437-Amino-3-methoxy-3-cephem-4-carboxylic acid hydrochloride

Product 1

HCID 1317124397-[2-{2-(2,2,2-Trifluoroacetamido)-4-thiazolyl}--methoxyiminoacetamido]-3-methoxy-3-cephem-4-carboxylic acidYield 26.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of 2-{2-(2,2,2-trifluoroacetamido)-4-thiazolyl}-2-methoxyiminoacetic acid (syn isomer, 0.8 g.), dimethylformamide (0.20 g.), phosphorus oxychloride (0.41 g.) and ethyl acetate (10 ml.) was stirred for 30 minutes under ice-cooling to prepare the activated acid solution in a similar manner to that of Example 2-(1). On the other hand, a solution of 7-amino-3-methoxy-3-cephem-4-carboxylic acid hydrochloride (0.6 g.) and trimethylsilylacetamide (3 g.) in ethyl acetate (15 ml.) was stirred at 40° C. for 3 hours. To the solution was added dropwise the activated acid solution at -10° to -20° C. in 2 minutes, and the mixture was stirred at the same temperature for 1.5 hours. After water (10 ml.) was added to the resultant mixture, the ethyl acetate layer was separated and allowed to stand. The precipitates were collected by filtration to give 7-[2-{ 2-(2,2,2-trifluoroacetamido)-4-thiazolyl}-2-methoxyiminoacetamido]-3-methoxy-3-cephem-4-carboxylic acid (syn isomer, 0.3 g.). The aqueous layer, which was separated from the ethyl acetate layer, was extracted with ethyl acetate, and the extract was combined with the mother liquor obtained above. The ethyl acetate solution was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was washed with diethyl ether to give the same object compound (0.25 g.), Total yield 0.55 g.

Workup

  1. temperaturecooling
  2. customto prepare the activated acid solution in a similar manner to that of Example 2-(1)
  3. additionTo the solution was added dropwise the activated acid solution at -10° to -20° C. in 2 minutes
  4. stirringthe mixture was stirred at the same temperature for 1.5 hours
  5. customthe ethyl acetate layer was separated
  6. filtrationThe precipitates were collected by filtration

Sources & evidence

ORD record
ord-addc4203bd4d44278e9e92d752440b23
Source dataset
uspto-grants-1986_08
Patent number
US04604456

Reaction notes

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