Phosphorus oxychloride → 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-hydroxy-2-(2-formylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

HRID 638447Notes

Reaction equation

HRID 638447 reaction equation
P(Cl)(Cl)(Cl)=O.[OH:6][CH:7]([C:11]1[N:12]=[C:13]([NH:16][CH:17]=[O:18])[S:14][CH:15]=1)[C:8]([OH:10])=O.[CH3:19][N:20]1[C:24]([S:25][CH2:26][C:27]2[CH2:28][S:29][C@@H:30]3[CH:37]([NH2:38])[C:36](=[O:39])[N:31]3[C:32]=2[C:33]([OH:35])=[O:34])=[N:23][N:22]=[N:21]1.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>C(Cl)Cl.CN(C)C=O>[CH3:19][N:20]1[C:24]([S:25][CH2:26][C:27]2[CH2:28][S:29][C@@H:30]3[CH:37]([NH:38][C:8](=[O:10])[CH:7]([OH:6])[C:11]4[N:12]=[C:13]([NH:16][CH:17]=[O:18])[S:14][CH:15]=4)[C:36](=[O:39])[N:31]3[C:32]=2[C:33]([OH:35])=[O:34])=[N:23][N:22]=[N:21]1

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 11708267BistrimethylsilylacetamidHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 202543512-Hydroxy-2-(2-formylaminothiazol-4-yl)acetic acid

Product 1

HCID 704908713-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-hydroxy-2-(2-formylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

To dimethylformamide (5 ml.) was dropwise added phosphorus oxychloride (0.794 g.) under stirring and ice-cooling, and the mixture was stirred for 30 minutes at 40° C., and then cooled to -20° C. To the mixture was gradually added 2-hydroxy-2-(2-formylamino-1,3-thiazol-4-yl)acetic acid, which can be represented as 2-hydroxy-2-(2-formylimino-2,3-dihydro-1,3-thiazol-4-yl)acetic acid, (0.505 g.) at -20° C., and the mixture was stirred for 45 minutes at -12° to -10° C. Thus obtained mixture was added to a solution, which was prepared by stirring a mixture of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (0.804 g.), bis(trimethylsilyl)acetamide (2.62 ml.) in methylene chloride (15 ml.) for an hour at room temperature and for 2 hours at 35° to 40° C. and then by cooling it to -30° C., at a time. The mixture was stirred for an hour at -20° to -15° C., and then methylene chloride was distilled off. The resulting residue was purified by a conventional manner to give 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-hydroxy-2-(2-formylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-hydroxy-2-(2-formylimino-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, (0.51 g.).

Workup

  1. temperatureice-cooling
  2. stirringthe mixture was stirred for 30 minutes at 40° C.
  3. stirringthe mixture was stirred for 45 minutes at -12° to -10° C
  4. additionThus obtained mixture was added to a solution, which
  5. customwas prepared
  6. stirringby stirring
  7. temperatureby cooling it to -30° C.
  8. stirringThe mixture was stirred for an hour at -20° to -15° C.
  9. distillationmethylene chloride was distilled off
  10. customThe resulting residue was purified by a conventional manner

Sources & evidence

ORD record
ord-ae1e3f69c13b43ecaca19bc74eb0be9c
Source dataset
uspto-grants-1985_12
Patent number
US04560765

Reaction notes

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