Phosphorus oxychloride → HCID 131712301, compound

HRID 1278153Notes

Reaction equation

HRID 1278153 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][N:8]=[C:9]([C:13]1[N:14]=[C:15]([NH2:18])[S:16][CH:17]=1)[C:10]([OH:12])=O.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[NH2:31][CH:32]1[C:55](=[O:56])[N:34]2[C:35]([C:52]([OH:54])=[O:53])=[C:36]([CH2:39][O:40][C:41](=[O:51])[C:42]3[CH:47]=[CH:46][C:45]([N+:48]([O-:50])=[O:49])=[CH:44][CH:43]=3)[CH2:37][S:38][C@H:33]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CN(C)C=O>[CH3:6][O:7][N:8]=[C:9]([C:13]1[N:14]=[C:15]([NH2:18])[S:16][CH:17]=1)[C:10]([NH:31][CH:32]1[C:55](=[O:56])[N:34]2[C:35]([C:52]([OH:54])=[O:53])=[C:36]([CH2:39][O:40][C:41](=[O:51])[C:42]3[CH:43]=[CH:44][C:45]([N+:48]([O-:50])=[O:49])=[CH:46][CH:47]=3)[CH2:37][S:38][C@H:33]12)=[O:12]

Participants

9

Reactant 6

HCID 24813Phosphorus oxychloride2×HCID 1252162-(2-Aminothiazole-4-yl)-2-methoxyiminoacetic acidHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 11708267BistrimethylsilylacetamidHCID 70491940HCID 70491940, compound

Product 1

HCID 131712301HCID 131712301, compoundYield 42.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Phosphorus oxychloride (0.56 g) was at a time added under 5° C. to a mixture of 2-methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetic acid (syn isomer) (0.6 g) and dry ethyl acetate (6 ml), and the mixture was stirred for 20 minutes at 4° to 6° C. Bis(trimethylsilyl)acetamide (0.3 g) was at a time added thereto at the same temperature and the mixture was stirred for 10 minutes at the same temperature.To the resulting mixture was at a time added phosphorus oxychloride (0.56 g) and the mixture was stirred for 30 minutes at the same temperature, to which was added dropwise dimethylformamide (0.24 g) and the resulting mixture was stirred for 30 minutes at 4° to 6° C. Thus obtained solution was at a time added with stirring at -15° C. to a solution of 7-amino-3-(4-nitrobenzoyl)oxymethyl-3-cephem-4-carboxylic acid (1.1 g) and trimethylsilylacetamide (3.5 g) in dry ethyl acetate (20 ml), and the resulting mixture was stirred for 2 hours at -5° to -10° C. The reaction mixture was adjusted to pH 7-7.5 with a saturated aqueous solution of sodium bicarbonate under 0° C., stirred for 1 hour at pH 7 under 5° C., adjusted to pH 2.5 and filtered. The organic layer in the filtrate was separated, and water (20 ml) was added thereto. The mixture was adjusted to pH 6.5 with sodium bicarbonate. The aqueous layer was separated and washed with diethyl ether. Remaining solvent in the aqueous layer was removed by passing nitrogen gas, and the aqueous layer was adjusted to pH 2.5 with 10% hydrochloric acid under ice-cooling. Precipitates were collected by filtration, washed with water and dried to give pale yellow powder of 7-[2-methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetamido]-3-(4-nitrobenzoyl)oxymethyl-3-cephem-4-carboxylic acid (syn isomer) (0.7 g), mp 151° to 163° C. (dec.).

Workup

  1. additionadded
  2. stirringat the same temperature and the mixture was stirred for 10 minutes at the same temperature.To the resulting mixture
  3. stirringthe mixture was stirred for 30 minutes at the same temperature, to which
  4. stirringthe resulting mixture was stirred for 30 minutes at 4° to 6° C
  5. additionadded
  6. stirringthe resulting mixture was stirred for 2 hours at -5° to -10° C
  7. stirringstirred for 1 hour at pH 7 under 5° C.
  8. filtrationfiltered
  9. customThe organic layer in the filtrate was separated
  10. additionwater (20 ml) was added
  11. customThe aqueous layer was separated
  12. washwashed with diethyl ether
  13. customRemaining solvent in the aqueous layer was removed
  14. temperaturecooling
  15. customPrecipitates
  16. filtrationwere collected by filtration
  17. washwashed with water
  18. customdried

Sources & evidence

ORD record
ord-7f8e92a09adf4c4b8b8315fbcdb99233
Source dataset
uspto-grants-1981_07
Patent number
US04279818

Reaction notes

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