Phosphorus oxychloride → HCID 131712380, compound

HRID 2231424Notes

Reaction equation

HRID 2231424 reaction equation
P(Cl)(Cl)(Cl)=O.[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][C:13]([CH2:15][O:16][N:17]=[C:18]([C:22]2[N:23]=[C:24]([NH:27][CH:28]=[O:29])[S:25][CH:26]=2)[C:19]([OH:21])=O)=[O:14])[CH:7]=1.[NH2:30][CH:31]1[C:49](=[O:50])[N:33]2[C:34]([C:46]([OH:48])=[O:47])=[C:35]([CH2:38][S:39][C:40]3[N:44]([CH3:45])[N:43]=[N:42][N:41]=3)[CH2:36][S:37][C@H:32]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C)C=O>[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][C:13]([CH2:15][O:16][N:17]=[C:18]([C:22]2[N:23]=[C:24]([NH:27][CH:28]=[O:29])[S:25][CH:26]=2)[C:19]([NH:30][CH:31]2[C:49](=[O:50])[N:33]3[C:34]([C:46]([OH:48])=[O:47])=[C:35]([CH2:38][S:39][C:40]4[N:44]([CH3:45])[N:43]=[N:42][N:41]=4)[CH2:36][S:37][C@H:32]23)=[O:21])=[O:14])[CH:7]=1

Participants

8

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 54002447HCID 54002447, compound

Product 1

HCID 131712380HCID 131712380, compoundYield 34.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of phosphorus oxychloride (1.6 g.) and N,N-dimethylformamide (31 ml.) was warmed at 40° C. for 30 minutes followed by cooling to -10° C. To the mixture was added 2-[N-(3-pyridyl)carbamoylmethoxyimino]-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (3.1 g.) followed by stirring for an hour at -10° to -7° C. On the other hand, a mixture of 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (3.2 g.) and trimethylsilylacetamide (7 g.) in methylene chloride (60 ml.) was stirred for 30 minutes at room temperature and then cooled to -15° C. To the mixture was added the above obtained dimethylformamide mixture followed by stirring for 1.5 hours at -15° to -10° C. To the reaction mixture were added ice-cold water and sodium bicarbonate. The aqueous layer (pH 7 to 8) was separated and washed with ethyl acetate and then thereto was added ethyl acetate. After the pH was adjusted to 3 to 4 with 10% hydrochloric acid, the precipitates were collected and then dissolved in an aqueous solution of sodium bicarbonate. The resulting mixture was treated with activated charcoal and the aqueous layer was separated and then adjusted to pH 3 to 4 with 10% hydrochloric acid. The precipitates were collected by filtration and dried to give the title compound (2.0 g.).

Workup

  1. temperatureby cooling to -10° C
  2. stirringwas stirred for 30 minutes at room temperature
  3. temperaturecooled to -15° C
  4. additionTo the mixture was added the
  5. stirringby stirring for 1.5 hours at -15° to -10° C
  6. customThe aqueous layer (pH 7 to 8) was separated
  7. washwashed with ethyl acetate
  8. additionwas added ethyl acetate
  9. customthe precipitates were collected
  10. dissolutiondissolved in an aqueous solution of sodium bicarbonate
  11. additionThe resulting mixture was treated with activated charcoal
  12. customthe aqueous layer was separated
  13. filtrationThe precipitates were collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-ee9edefaf83f4640868a866654552af3
Source dataset
uspto-grants-1988_11
Patent number
US04782158

Reaction notes

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