Phosphorus oxychloride → 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-hexyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 2412793Notes

Reaction equation

HRID 2412793 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH3:6][O:7][N:8]=[C:9]([C:13]1[N:14]=[C:15]([NH:18][CH:19]=[O:20])[S:16][CH:17]=1)[C:10]([OH:12])=O.[NH2:21][CH:22]1[C:45](=[O:46])[N:24]2[C:25]([C:42]([OH:44])=[O:43])=[C:26]([CH2:29][S:30][C:31]3[N:35]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[N:34]=[N:33][N:32]=3)[CH2:27][S:28][C@H:23]12.C[Si](CC(N)=O)(C)C>O.C(OCC)(=O)C.CN(C)C=O>[CH3:23][N+:24]([CH3:45])=[CH:25][Cl:3].[Cl-:3].[CH3:6][O:7][N:8]=[C:9]([C:13]1[N:14]=[C:15]([NH:18][CH:19]=[O:20])[S:16][CH:17]=1)[C:10]([NH:21][CH:22]1[C:45](=[O:46])[N:24]2[C:25]([C:42]([OH:44])=[O:43])=[C:26]([CH2:29][S:30][C:31]3[N:35]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[N:34]=[N:33][N:32]=3)[CH2:27][S:28][C@H:23]12)=[O:12]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 704323317-amino-3-(1-hexyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317126017-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-hexyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 179.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
40 °C

Procedure

The Vilsmeier reagent was prepared from dry dimethylformamide (1.0 g.), dry ethyl acetate (4 ml.) and phosphorus oxychloride (2.1 g.) by the conventional method. Dry ethyl acetate (45 ml.) and 2-methoxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (2.85 g.) were added thereto. This solution was added at -10° C. to a stirred solution, which was prepared by stirring for 1 hour at 40° C. a mixture of 7-amino-3-(1-hexyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (4.5 g.), trimethylsilylacetamide (10.4 g.) and dry ethyl acetate (90 ml.), and the resulting mixture was stirred for 1.5 hours at -5° to -10° C. Water (50 ml.) was added to the reaction mixture and the ethyl acetate layer was separated. Water (40 ml.) was added thereto and the mixture was adjusted to pH 7.0 with a saturated aqueous solution of sodium bicarbonate. The aqueous layer was separated, washed with ethyl acetate and adjusted to pH 2.5 with 10% hydrochloric acid. Precipitates were collected by filtration, washed with water and dried under reduced pressure to give powder of 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-hexyl- 1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (6.18 g.).

Workup

  1. additionThis solution was added at -10° C. to a stirred solution, which
  2. customwas prepared
  3. stirringthe resulting mixture was stirred for 1.5 hours at -5° to -10° C
  4. customthe ethyl acetate layer was separated
  5. additionWater (40 ml.) was added
  6. customThe aqueous layer was separated
  7. washwashed with ethyl acetate
  8. customPrecipitates
  9. filtrationwere collected by filtration
  10. washwashed with water
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-ad8dad40004947969726b4e320d4a4ad
Source dataset
uspto-grants-1985_01
Patent number
US04493833

Reaction notes

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