Phosphorus oxychloride → 7-{2-[2-Amino-1,3-thiazol-4-yl]-2-[3-(3,4-diacetoxybenzoyl)carbazoyl]methoxyiminoacetamido}-3-[(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid 1-ethoxycarbonyloxyethyl ester

HRID 1383128Notes

Reaction equation

HRID 1383128 reaction equation
[Na+].C([NH:4][C:5]1[S:6][CH:7]=[C:8]([C:10](=[N:34][O:35][CH2:36][C:37](=[O:42])[NH:38][NH:39][CH:40]=[O:41])[C:11]([NH:13][CH:14]2[C:32](=[O:33])[N:16]3[C:17]([C:29]([O-:31])=[O:30])=[C:18]([CH2:21][S:22][C:23]4[S:24][C:25]([CH3:28])=[N:26][N:27]=4)[CH2:19][S:20][C@H:15]23)=[O:12])[N:9]=1)=O.P(Cl)(Cl)(Cl)=O.[CH3:48]/[C:49](/[O:55][Si](C)(C)C)=N\[Si](C)(C)C.[C:60]([O:63][C:64]1[CH:65]=[C:66]([CH:70]=[CH:71][C:72]=1[O:73][C:74](=[O:76])[CH3:75])C(Cl)=O)(=[O:62])[CH3:61]>CN(C=O)C.CCOCC.C(OCC)(=O)C>[CH2:49]([O:55][C:60]([O:63][CH:64]([O:31][C:29]([C:17]1[N:16]2[C:32](=[O:33])[CH:14]([NH:13][C:11](=[O:12])[C:10]([C:8]3[N:9]=[C:5]([NH2:4])[S:6][CH:7]=3)=[N:34][O:35][CH2:36][C:37](=[O:42])[NH:38][NH:39][C:40](=[O:41])[C:66]3[CH:70]=[CH:71][C:72]([O:73][C:74](=[O:76])[CH3:75])=[C:64]([O:63][C:60](=[O:62])[CH3:61])[CH:65]=3)[C@H:15]2[S:20][CH2:19][C:18]=1[CH2:21][S:22][C:23]1[S:24][C:25]([CH3:28])=[N:26][N:27]=1)=[O:30])[CH3:72])=[O:62])[CH3:48]

Participants

8

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 140969484-(Chlorocarbonyl)-1,2-phenylene diacetateHCID 1317158777-[2-(2-Formylamino-1,3-thiazol-4-yl)-2-(3-formylcarbazoyl)methoxyiminoacetoamido]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid sodium salt

Product 1

HCID 1317158767-{2-[2-Amino-1,3-thiazol-4-yl]-2-[3-(3,4-diacetoxybenzoyl)carbazoyl]methoxyiminoacetamido}-3-[(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid 1-ethoxycarbonyloxyethyl esterYield 190.3%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 40 ml of DMF was dissolved 6.309 g (9.5 mmole) of 7-[2-(2-formylamino-1,3-thiazol-4-yl)-2-(3-formylcarbazoyl)methoxyiminoacetoamido]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid sodium salt and the mixture was ice-cooled, and 4.88 g (20 mmole) of 1-iododiethylcarbonate was added thereto and stirred at room temperature for 3 hours. To the resulting mixture was added 700 ml of ethyl acetate and the mixture was washed with water and then washed with a saturated saline solution, dried over anhydrous magnesium sulfate and the solvent was distilled out. The residue was purified through silica gel column chromatography (eluent: 5% to 10% methanol-chloroform). To 30 ml of ice-cooled methanol was added 0.92 g (6 mmole) of phosphorus oxychloride and then purified product through column, and the mixture was stirred for 1.5 hours under ice-cooling. The resulting mixture was added dropwise into 800 ml of ether while vigorously stirring and resulting precipitates were collected by filtration and dried. After the resulting product was dissolved in 30 ml of methylene chloride and ice-cooled, 25 ml (10 mmole) of N,O-bis(trimethylsilyl)acetamide was added thereto and the mixture was stirred for 10 minutes. Then, 0.9 g (3.5 mmole) of 3,4-diacetoxybenzoic acid chloride was added thereto and the mixture was stirred for one hour under ice-cooling. The resulting mixture was added dropwise into 800 ml of ether and resulting precipitates were collected by filtration, washed with ether and then dried to obtain 3.07 g of the title compound. (Yield: 35.5%)

Workup

  1. temperaturecooled
  2. washthe mixture was washed with water
  3. washwashed with a saturated saline solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled out
  6. customThe residue was purified through silica gel column chromatography (eluent: 5% to 10% methanol-chloroform)
  7. temperatureTo 30 ml of ice-cooled methanol
  8. stirringpurified product through column, and the mixture was stirred for 1.5 hours under ice-
  9. temperaturecooling
  10. stirringwhile vigorously stirring
  11. customresulting
  12. customprecipitates
  13. filtrationwere collected by filtration
  14. customdried
  15. dissolutionAfter the resulting product was dissolved in 30 ml of methylene chloride
  16. temperatureice-cooled
  17. stirringthe mixture was stirred for 10 minutes
  18. stirringthe mixture was stirred for one hour under ice-
  19. temperaturecooling
  20. customresulting
  21. customprecipitates
  22. filtrationwere collected by filtration
  23. washwashed with ether
  24. customdried

Sources & evidence

ORD record
ord-71e655a6331842099c78181cd3debf9a
Source dataset
uspto-grants-1989_02
Patent number
US04808711

Reaction notes

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