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

HRID 1982658Notes

Reaction equation

HRID 1982658 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[N:14]=[C:13]([C:15](=[N:19][O:20]C(=O)C(Cl)Cl)[C:16]([OH:18])=O)[CH:12]=[CH:11][CH:10]=1)=[O:7].[NH2:26][CH:27]1[C:45](=[O:46])[N:29]2[C:30]([C:42]([OH:44])=[O:43])=[C:31]([CH2:34][S:35][C:36]3[N:40]([CH3:41])[N:39]=[N:38][N:37]=3)[CH2:32][S:33][C@H:28]12>CN(C)C=O.C[Si](CC(N)=O)(C)C.C(Cl)Cl>[CH:6]([NH:8][C:9]1[N:14]=[C:13]([C:15](=[N:19][OH:20])[C:16]([NH:26][CH:27]2[C:45](=[O:46])[N:29]3[C:30]([C:42]([OH:44])=[O:43])=[C:31]([CH2:34][S:35][C:36]4[N:40]([CH3:41])[N:39]=[N:38][N:37]=4)[CH2:32][S:33][C@H:28]23)=[O:18])[CH:12]=[CH:11][CH:10]=1)=[O:7]

Participants

7

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 540135142-(6-Formamidopyridin-2-yl)-2-dichloroacetoxyiminoacetic acid

Product 1

HCID 1371959547-[2-(6-formamidopyridin-2-yl)-2-hydroxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 68.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 357676Acetamide, 2-(trimethylsilyl)-Solvent

Procedure

A solution of phosphoryl chloride (2.14 g.) in N,N-dimethylformamide (14 ml.) was stirred at 37° to 40° C. for 30 minutes. To the solution were added methylene chloride (14 ml.) and 2-(6-formamidopyridin-2-yl)-2-dichloroacetoxyiminoacetic acid (syn isomer) (4.48 g.) at -20° to -25° C. and stirred at -10° to -15° C. for 30 minutes [solution A]. On the other hand, 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (4.6 g.) was dissolved in a solution of trimethylsilylacetamide (14 g.) in methylene chloride (150 ml.) at 40° C., and cooled to -10° to -15° C. The solution was added to the above solution A at -10° to -15° C. and stirred at the same temperature for 30 minutes. After removing methylene chloride from the resultant solution under reduced pressure, ice water and ethyl acetate were added to the residue, and adjusted to pH 4 with an aqueous solution of sodium bicarbonate. The aqueous layer was separated, washed with ethyl acetate, adjusted to pH 2 with 10% hydrochloric acid, and then extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was triturated with diethyl ether. The precipitates were collected by filtration; washed with diethyl ether and dired to give 7-[2-(6-formamidopyridin-2-yl)-2-hydroxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (5.0 g.), mp. 110° to 115° C.

Workup

  1. temperaturecooled to -10° to -15° C
  2. customAfter removing methylene chloride from the resultant solution under reduced pressure, ice water and ethyl acetate
  3. additionwere added to the residue
  4. customThe aqueous layer was separated
  5. washwashed with ethyl acetate
  6. extractionextracted with ethyl acetate
  7. washThe extract was washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was triturated with diethyl ether
  11. filtrationThe precipitates were collected by filtration
  12. washwashed with diethyl ether

Sources & evidence

ORD record
ord-af635831e9f64d0193247148472dd40c
Source dataset
uspto-grants-1986_06
Patent number
US04596869

Reaction notes

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