Phosphorus oxychloride → 7-[2-(2-Formamidothiazol-4-yl)-2-(2-azidoethoxyimino)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 255760Notes

Reaction equation

HRID 255760 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][N:17]=[N+:18]=[N-:19])[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.[NH2:25][CH:26]1[C:43](=[O:44])[N:28]2[C:29]([C:40]([OH:42])=[O:41])=[C:30]([CH2:33][S:34][C:35]3[S:36][CH:37]=[N:38][N:39]=3)[CH2:31][S:32][C@H:27]12.C[Si](CC(N)=O)(C)C>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][N:17]=[N+:18]=[N-:19])[C:10]([NH:25][CH:26]2[C:43](=[O:44])[N:28]3[C:29]([C:40]([OH:42])=[O:41])=[C:30]([CH2:33][S:34][C:35]4[S:36][CH:37]=[N:38][N:39]=4)[CH2:31][S:32][C@H:27]23)=[O:12])[N:8]=1)=[O:2]

Participants

8

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 128891877-Amino-3-(1,3,4-thiadiazol-2-ylthiomethyl)-3cephem-4-carboxylic acidHCID 538311562-(2-Formamidothiazol-4-yl)-2-(2-azidoethoxyimino)acetic acid

Product 1

HCID 1317152867-[2-(2-Formamidothiazol-4-yl)-2-(2-azidoethoxyimino)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acidYield 80.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

2-(2-Formamidothiazol-4-yl)-2-(2-azidoethoxyimino)acetic acid (syn isomer, 0.70 g.), N,N-dimethylformamide (0.21 ml.), phosphoryl chloride (0.4 g.) and ethyl acetate (15.8 ml.) were treated in a similar manner to that of Example 1-(1) to give an activated acid solution. The solution was added to a solution of 7-amino-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (0.74 g.) and trimethylsilylacetamide (2.0 g.) in ethyl acetate (15 ml.) at -10° to -15° C. and stirred at the same temperature for an hour. After adding water (30 ml.) to the resultant solution, the organic layer was separated, washed with a saturated aqueous solution of sodium chloride dried over magnesium sulfate and evaporated in vacuo to give 7-[2-(2-formamidothiazol-4-yl)-2-(2-azidoethoxyimino)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 1.08 g.).

Workup

  1. customto give an activated acid solution
  2. customthe organic layer was separated
  3. washwashed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-18f219bb819d42789cb9f54a0de61cd8
Source dataset
uspto-grants-1987_10
Patent number
US04698337

Reaction notes

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