Pyridine → benzhydryl 7-amino-3-[(Z)-2-(4-methyl-1,2,3-thiadiazol-5-yl)vinyl]-3-cephem-4-carboxylate

HRID 1461170Notes

Reaction equation

HRID 1461170 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.N1C=CC=CC=1.C1(CC([NH:22][CH:23]2[C:54](=[O:55])[N:25]3[C:26]([C:38]([O:40][CH:41]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)=[O:39])=[C:27]([CH:30]=[CH:31][C:32]4[S:36][N:35]=[N:34][C:33]=4[CH3:37])[CH2:28][S:29][C@H:24]23)=O)C=CC=CC=1.C(=O)(O)[O-].[Na+]>O.CO.C(Cl)Cl>[NH2:22][CH:23]1[C:54](=[O:55])[N:25]2[C:26]([C:38]([O:40][CH:41]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[O:39])=[C:27](/[CH:30]=[CH:31]\[C:32]3[S:36][N:35]=[N:34][C:33]=3[CH3:37])[CH2:28][S:29][C@H:24]12

Participants

8

Reactant 4

HCID 1049PyridineHCID 24819Phosphorus pentachlorideHCID 516892Sodium BicarbonateHCID 131717108Benzhydryl 7-phenylacetamido-3-[2-(4-methyl-1,2,3-thiadiazol-5-yl)vinyl]-3-cephem-4-carboxylate

Product 1

HCID 14621702benzhydryl 7-amino-3-[(Z)-2-(4-methyl-1,2,3-thiadiazol-5-yl)vinyl]-3-cephem-4-carboxylateYield 45%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Phosphorus pentachloride (5.83 g, 28 mmol) was made a methylene chloride (50 ml) suspension, pyridine (7.39 g, 93 mmol) was added at 5°-10° C. and stirring was continued for 40 minutes. Added all at once at 5° C. thereto was benzhydryl 7-phenylacetamido-3-[2-(4-methyl-1,2,3-thiadiazol-5-yl)vinyl]-3-cephem-4-carboxylate (E/Z=1/3.5, 5.69 g, 9.36 mmol), and the mixture was stirred at the same temperature for 3 hours. Methanol (38 ml) was slowly added to the reaction mixture at -50° C., and it was stirred for 1 hour at -50° to -30° C. Water (7 ml) was added at -10° C. and the reaction temperature was set at 0° C. and then it was stirred for 10 minutes. The reaction solution was adjusted to pH 6 with saturated sodium bicarbonate solution and then extracted with methylene chloride. It was washed with water and then the methylene chloride layer was dried over magnesium sulfate. The solvent was distilled off and then ethyl acetate was added to the residue. Precipitates were filtered and then cleansed with ethyl acetate thereby benzhydryl 7-amino-3-[(Z)-2-(4-methyl-1,2,3-thiadiazol-5-yl)vinyl]-3-cephem-4-carboxylate (2.06 g, 45% yield) was obtained.

Workup

  1. additionwas added at 5°-10° C.
  2. additionAdded all at once at 5° C.
  3. stirringthe mixture was stirred at the same temperature for 3 hours
  4. stirringit was stirred for 1 hour at -50° to -30° C
  5. customwas set at 0° C.
  6. stirringit was stirred for 10 minutes
  7. extractionextracted with methylene chloride
  8. washIt was washed with water
  9. dry with materialthe methylene chloride layer was dried over magnesium sulfate
  10. distillationThe solvent was distilled off
  11. additionethyl acetate was added to the residue
  12. customPrecipitates
  13. filtrationwere filtered

Sources & evidence

ORD record
ord-0cdb750bb18843eb9c78b670013814ba
Source dataset
uspto-grants-1991_12
Patent number
US05073551

Reaction notes

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