Phosphorus oxychloride → 7-[2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 1075227Notes

Reaction equation

HRID 1075227 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[N:14]=[C:13]([C:15](=[N:19][O:20][CH3:21])[C:16]([OH:18])=O)[CH:12]=[CH:11][CH:10]=1)=[O:7].[NH2:22][CH:23]1[C:41](=[O:42])[N:25]2[C:26]([C:38]([OH:40])=[O:39])=[C:27]([CH2:30][S:31][C:32]3[N:36]([CH3:37])[N:35]=[N:34][N:33]=3)[CH2:28][S:29][C@H:24]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(Cl)Cl.O>[CH:6]([NH:8][C:9]1[N:14]=[C:13]([C:15](=[N:19][O:20][CH3:21])[C:16]([NH:22][CH:23]2[C:41](=[O:42])[N:25]3[C:26]([C:38]([OH:40])=[O:39])=[C:27]([CH2:30][S:31][C:32]4[N:36]([CH3:37])[N:35]=[N:34][N:33]=4)[CH2:28][S:29][C@H:24]23)=[O:18])[CH:12]=[CH:11][CH:10]=1)=[O:7]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 543262512-(6-Formamidopyridin-2-yl)-2-methoxyiminoacetic acid

Product 1

HCID 1317122187-[2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 32.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

Phosphoryl chloride (0.998 g.) was added to N,N-dimethylformamide (5 ml.) and stirred at 40° C. for 30 minutes. To the solution was added a solution of 2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetic acid (syn isomer) (1.125 g.) in N,N-dimethylformamide (5 ml.) at -15° C., and stirred at -10° to -8° C. for 50 minutes [solution A]. On the other hand, 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (2.007 g.) and trimethylsilylacetamide (7.22 g.) were dissolved in methylene chloride (20 ml.) at 40° C. and cooled. To the cool solution was added the above solution A at -20° to -15° C. and stirred at the same temperature for 40 minutes. The resultant solution was poured into a solution of a saturated aqueous solution of sodium bicarbonate (30 ml.) and water (40 ml.) under ice cooling. The aqueous layer was separated, washed with ethyl acetate, and then ethyl acetate (50 ml.) was added to the aqueous layer. The solution was adjusted to pH 3 with 10% hydrochloric acid, and extracted with ethyl acetate twice. The extract was washed with water and concentrated to a small amount under reduced pressure. The appeared precipitates were collected by filtration, washed with ethyl acetate and dried to give 7-[2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (873 mg.). The same product (126 mg.) was recovered from the mother liquor. Total yield was 999 mg.

Workup

  1. temperaturecooled
  2. stirringstirred at the same temperature for 40 minutes
  3. customThe aqueous layer was separated
  4. washwashed with ethyl acetate
  5. additionethyl acetate (50 ml.) was added to the aqueous layer
  6. extractionextracted with ethyl acetate twice
  7. washThe extract was washed with water
  8. concentrationconcentrated to a small amount under reduced pressure
  9. customThe appeared precipitates
  10. filtrationwere collected by filtration
  11. washwashed with ethyl acetate
  12. customdried

Sources & evidence

ORD record
ord-4984bcb9b686427b98981f0fa6303ca4
Source dataset
uspto-grants-1983_07
Patent number
US04395411

Reaction notes

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