Phosphorus oxychloride → HCID 178502762, compound

HRID 1982665Notes

Reaction equation

HRID 1982665 reaction equation
P(Cl)(Cl)(Cl)=O.[NH2:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([C:13](=[N:17][O:18][CH3:19])[C:14]([OH:16])=O)[N:8]=1.[NH2:20][CH:21]1[C:39](=[O:40])[N:23]2[C:24]([C:36]([OH:38])=[O:37])=[C:25]([CH:28]([S:30][C:31]3[NH:35][N:34]=[N:33][N:32]=3)[CH3:29])[CH2:26][S:27][C@H:22]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.CN(C)C=O>[NH2:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([C:13](=[N:17][O:18][CH3:19])[C:14]([NH:20][CH:21]2[C:39](=[O:40])[N:23]3[C:24]([C:36]([OH:38])=[O:37])=[C:25]([CH:28]([S:30][C:31]4[NH:32][N:33]=[N:34][N:35]=4)[CH3:29])[CH2:26][S:27][C@H:22]23)=[O:16])[N:8]=1

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 54097963HCID 54097963, compoundHCID 1784773817-Amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid

Product 1

HCID 178502762HCID 178502762, compoundYield 19.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-20 °C

Procedure

Phosphoryl chloride (500 mg.) was added dropwise to a suspension of 2-(4-aminopyrimidin-2-yl)-2-methoxyiminoacetic acid (syn isomer) (250 mg.) in ethyl acetate (5 ml.) at 0° to 6° C. with stirring and the stirring was continued at the same temperature for 45 minutes. To this solution was added dropwise N,N-dimethylformamide (0.7 ml.) over a period of 6 minutes at 0° to 6° C. with stirring, and the stirring was continued at the same temperature for 40 minutes. To the resultant solution was added all at once a solution of 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (365 mg.) and trimethylsilylacetamide (1.5 g.) in ethyl acetate (7 ml.) under cooling at -20° C., and the mixture was stirred at 0° to 6° C. for an hour. The reaction mixture was poured into water (20 ml.) and adjusted to pH 4 with an aqueous solution of sodium bicarbonate. The aqueous layer was separated out and the remaining organic layer was extracted with water. The aqueous layers were combined together and the ethyl acetate remained in the aqueous solution was removed therefrom under reduced pressure. The aqueous solution was subjected to column chromatography on a non-ionic adsorption resin, "Diaion HP-20" (Trade Mark, manufactured by Mitsubishi Chemical Industry Ltd.) (20 ml.). After the column was washed with water, elution was carried out with 5-10% aqueous methanol (100 ml.), 20% aqueous methanol (150 ml.) and 20 to 30% aqueous methanol (150 ml.) in turn, and the fractions containing the desired compound were collected and evaporated to dryness under reduced pressure. The resultant residue was lyophilized to give 7-[ 2-(4-aminopyrimidin-2-yl)-2-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (syn isomer) (110 mg.), mp. 155° to 158° C.

Workup

  1. stirringwith stirring
  2. waitthe stirring was continued at the same temperature for 40 minutes
  3. stirringthe mixture was stirred at 0° to 6° C. for an hour
  4. customThe aqueous layer was separated out
  5. extractionthe remaining organic layer was extracted with water
  6. customwas removed
  7. washAfter the column was washed with water, elution
  8. additionthe fractions containing the desired compound
  9. customwere collected
  10. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-1a6ae64dea6340b190b5188233a4d444
Source dataset
uspto-grants-1986_06
Patent number
US04596869

Reaction notes

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