Phosphorus oxychloride → HCID 70505148, compound

HRID 1659409Notes

Reaction equation

HRID 1659409 reaction equation
P(Cl)(Cl)(Cl)=O.[O:6]=[C:7]1[NH:11][C:10]([C:12](=[O:16])[C:13]([OH:15])=O)=[CH:9][S:8]1.[CH3:17][N:18]1[C:22]([S:23][CH2:24][C:25]2[CH2:26][S:27][C@@H:28]3[CH:35]([NH2:36])[C:34](=[O:37])[N:29]3[C:30]=2[C:31]([OH:33])=[O:32])=[N:21][N:20]=[N:19]1.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CN(C)C=O>[CH3:17][N:18]1[C:22]([S:23][CH2:24][C:25]2[CH2:26][S:27][C@@H:28]3[CH:35]([NH:36][C:13](=[O:15])[C:12]([C:10]4[NH:11][C:7](=[O:6])[S:8][CH:9]=4)=[O:16])[C:34](=[O:37])[N:29]3[C:30]=2[C:31]([OH:33])=[O:32])=[N:21][N:20]=[N:19]1

Participants

9

Reactant 6

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 11708267BistrimethylsilylacetamidHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 20254390HCID 20254390, compoundHCID 178525972HCID 178525972, compound

Product 1

HCID 70505148HCID 70505148, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-20 °C

Procedure

To dimethylformamide (3.74 g.) was dropwise added phosphorus oxychloride (6.46 g.) over 5 minutes under stirring and ice-cooling, and the mixture was stirred for 30 minutes at 40° C. To the mixture was added ethyl acetate (120 ml.) with stirring, and the mixture was cooled to -20° C. with stirring. To the mixture was added all at once 2-(2-oxo-2,3-dihydro-1,3-thiazol-4-yl)glyoxylic acid, which can be represented as 2-(2-hydroxy-1,3-thiazol-4-yl)glyoxylic acid, (6.05 g.) and to the mixture was added dimethylformamide (55 ml.) over 10 minutes at -20° C., and then the mixture was stirred for 40 minutes at the same temperature. Thus obtained mixture was added to the solution prepared in the similar manner as in Example 1 from 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7amino-3-cephem-4-carboxylic acid (10.50 g.), bis(trimethylsilyl)acetamide (35 ml.) and ethyl acetate (150 ml.), at - 50° to -40° C. with stirring. The mixture was stirred for 30 minutes at -40° C. and further stirred for 30 minutes at -20° C. After the reaction, the reaction mixture was poured into 5% sodium bicarbonate aqueous solution (250 ml.), and the aqueous layer was separated. The aqueous layer was washed with ethyl acetate and adjusted to pH 1 with 10% hydrochloric acid, and then extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and then treated with activated charcoal. After distillation of ethyl acetate from the extract, the residue was pulverized in diethyl ether, collected by filtration and dried to give pale yellow powder of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-oxo-2,3-dihydro-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4carboxylic acid, which can be represented as 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-hydroxy-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, (9.2 g.).

Workup

  1. customover 5 minutes
  2. temperatureice-cooling
  3. stirringthe mixture was stirred for 30 minutes at 40° C
  4. stirringwith stirring
  5. stirringwith stirring
  6. stirringthe mixture was stirred for 40 minutes at the same temperature
  7. additionThus obtained mixture was added to the solution
  8. stirringat - 50° to -40° C. with stirring
  9. stirringThe mixture was stirred for 30 minutes at -40° C.
  10. stirringfurther stirred for 30 minutes at -20° C
  11. customAfter the reaction
  12. customthe aqueous layer was separated
  13. washThe aqueous layer was washed with ethyl acetate
  14. extractionextracted with ethyl acetate
  15. washThe extract was washed with water
  16. dry with materialdried over magnesium sulfate
  17. additiontreated with activated charcoal
  18. distillationAfter distillation of ethyl acetate from the extract
  19. filtrationcollected by filtration
  20. customdried

Sources & evidence

ORD record
ord-7f61521bbe334cd7bbcf7c2396be1c3b
Source dataset
uspto-grants-1981_12
Patent number
US04303655

Reaction notes

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