Dacthal → HCID 70463764, compound

HRID 543534

Reaction equation

HRID 543534 reaction equation
CC(O[CH2:5][C:6]1[CH2:15][S:14][C@@H:9]2[C@H:10]([NH2:13])[C:11](=[O:12])[N:8]2[C:7]=1[C:16]([OH:18])=[O:17])=O.[SH:19][C:20]1[N:24]([CH3:25])[N:23]=[N:22][N:21]=1.COC(C1C([Cl:36])=C(Cl)C(C(OC)=O)=C(Cl)C=1Cl)=O>C(#N)C>[ClH:36].[NH2:13][CH:10]1[C:11](=[O:12])[N:8]2[C:7]([C:16]([OH:18])=[O:17])=[C:6]([CH2:5][S:19][C:20]3[N:24]([CH3:25])[N:23]=[N:22][N:21]=3)[CH2:15][S:14][C@H:9]12

Participants

5

Reactant 3

HCID 2943DacthalHCID 4413287-Aminocephalosporanic acidHCID 178482017HCID 178482017, compound

Product 1

HCID 70463764HCID 70463764, compoundYield 103.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
15 °C

Procedure

A 11 ml portion of acetonitrile was added to 2.72 g of 7-ACA and 1.28 g of 5-mercapto-1-methyl-1H-tetrazole, and 14.9 g of DCPA was added through a dropping funnel to the mixture with stirring and under cooling at -25° to -20° C., followed by rinsing the funnel with 1 ml of acetonitrile. The reaction mixture was warmed to 15° C., stirred at 14° to 16° C. for 40 minutes and cooled to -30° C., followed by adding dropwise 40 ml of ethanol at -30° to -20° C. The resultant solution was warmed to room temperature, and stirred under ice-cooling for 3.0 hours after the addition of 300 ml of methylene chloride, 100 ml of ether and 70 ml of ether saturated with water. The crystals separated out were recovered by filtration, washed with ether and dried, thereby affording 3.77 g (86.0% of purity as determined by high performance liquid chromatography, 88.9% of yield) of 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid hydrochloride.

Workup

  1. additionwas added through a dropping funnel to the mixture
  2. temperatureunder cooling at -25° to -20° C.
  3. washby rinsing the funnel with 1 ml of acetonitrile
  4. stirringstirred at 14° to 16° C. for 40 minutes
  5. temperaturecooled to -30° C.
  6. additionby adding dropwise 40 ml of ethanol at -30° to -20° C
  7. temperatureThe resultant solution was warmed to room temperature
  8. stirringstirred under ice-
  9. temperaturecooling for 3.0 hours
  10. additionafter the addition of 300 ml of methylene chloride, 100 ml of ether and 70 ml of ether saturated with water
  11. customThe crystals separated out
  12. filtrationwere recovered by filtration
  13. washwashed with ether
  14. customdried

Sources & evidence

ORD record
ord-46b479af67774d569c2efe4f247833c4
Source dataset
uspto-grants-1984_05
Patent number
US04446318

Linked notes

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