Hydrochloric Acid → 7-[2-benzyloxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 648417Notes

Reaction equation

HRID 648417 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:13][N:14]=[C:15]([C:19]1[N:20]=[C:21]([NH2:24])[S:22][CH:23]=1)[C:16]([OH:18])=O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C[Si](CC(N)=O)(C)C.[NH2:33][CH:34]1[C:55](=[O:56])[N:36]2[C:37]([C:52]([OH:54])=[O:53])=[C:38]([CH2:41][S:42][C:43]3[N:47]([CH2:48][C:49]([OH:51])=[O:50])[N:46]=[N:45][N:44]=3)[CH2:39][S:40][C@H:35]12.C(=O)(O)[O-].[Na+].Cl>O.C(O)(C)C.CC(C)=O.CN(C)C=O.O1CCCC1>[CH2:6]([O:13][N:14]=[C:15]([C:19]1[N:20]=[C:21]([NH2:24])[S:22][CH:23]=1)[C:16]([NH:33][CH:34]1[C:55](=[O:56])[N:36]2[C:37]([C:52]([OH:54])=[O:53])=[C:38]([CH2:41][S:42][C:43]3[N:47]([CH2:48][C:49]([OH:51])=[O:50])[N:46]=[N:45][N:44]=3)[CH2:39][S:40][C@H:35]12)=[O:18])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychloride2×HCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 127691497-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidHCID 541725632-(2-Aminothiazol-4-yl)-2-benzyloxyiminoacetic acid

Product 1

HCID 1317132197-[2-benzyloxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 31.1%

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Phosphorus oxychloride (0.8 g) was added at 0° C. to a mixture of 2-benzyloxyimino-2-(2-aminothiazol-4-yl)acetic acid (syn isomer) (1.1 g) and dry tetrahydrofuran (11.0 ml), and the mixture was stirred for 15 minutes at 0° C. Trimethylsilylacetamide (0.7 g) was added thereto and it was stirred for 15 minutes. Phosphorus oxychloride (0.8 g) was added thereto and it was stirred for 15 minutes. To the resulting mixture was added dry dimethylformamide (0.4 g) and it was stirred for 30 minutes at 0°-3° C. to give clear solution. On the other hand, acetone (9.0 ml) was added to a solution of 7-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.5 g) and sodium bicarbonate (1.0 g) in water (9.0 ml) and thereto was added the clear solution as obtained above at -3° to 3° C. and pH 7.5 to 8.5. The mixture was stirred for 1 hour at the same temperature and pH. An aqueous layer was separated and washed with ethyl acetate. After distilling off the remaining ethyl acetate, the aqueous layer was adjusted to pH 5.0 with 10% hydrochloric acid and subjected to column chromatography on Diaion HP-20 resin (Trademark: prepared by Mitsubishi Chemical Industries Ltd.) using 10% isopropyl alcohol as an eluent. The eluate was adjusted to pH 2.7 with 10% hydrochloric acid and precipitates were collected by filtration, washed with water and dried to give 7-[2-benzyloxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (0.78 g).

Workup

  1. stirringit was stirred for 15 minutes
  2. stirringit was stirred for 15 minutes
  3. stirringwas stirred for 30 minutes at 0°-3° C.
  4. customto give clear solution
  5. additionwas added the clear solution
  6. customas obtained above at -3° to 3° C. and pH 7.5 to 8.5
  7. stirringThe mixture was stirred for 1 hour at the same temperature and pH
  8. customAn aqueous layer was separated
  9. washwashed with ethyl acetate
  10. distillationAfter distilling off the remaining ethyl acetate
  11. customsubjected to column chromatography on Diaion HP-20 resin (Trademark: prepared by Mitsubishi Chemical Industries Ltd.)
  12. customprecipitates
  13. filtrationwere collected by filtration
  14. washwashed with water
  15. customdried

Sources & evidence

ORD record
ord-03bcfe8e020d4104906bf1d67ea5985a
Source dataset
uspto-grants-1983_10
Patent number
US04411898

Reaction notes

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