Phosphoric Acid → HCID 70636650, compound

HRID 435968Notes

Reaction equation

HRID 435968 reaction equation
[Na].C(O[CH2:6][C:7]1[CH2:14][S:13][CH:12]2[N:9]([C:10](=[O:25])[CH:11]2[NH:15][C:16](=[O:24])[CH2:17][C:18]2[S:19][CH2:20][CH2:21][S:22][CH:23]=2)[C:8]=1[C:26]([OH:28])=[O:27])(=O)C.[S-][C:30]#[N:31].[K+].P(=O)(O)(O)O>O.C(C(C)=O)C(C)C.N1C=CC=CC=1>[C:26]([C:8]1[N:9]2[CH:12]([S:13][CH2:14][C:7]=1[CH2:6][N+:31]1[CH:30]=[CH:26][CH:8]=[CH:7][CH:6]=1)[CH:11]([NH:15][C:16](=[O:24])[CH2:17][C:18]1[S:19][CH2:20][CH2:21][S:22][CH:23]=1)[C:10]2=[O:25])([O-:28])=[O:27]

Participants

8

Reactant 4

HCID 1004Phosphoric AcidHCID 516872Potassium thiocyanateHCID 5360545SodiumHCID 21454859HCID 21454859, compound

Product 1

HCID 70636650HCID 70636650, compoundYield 35.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 1049PyridineSolventHCID 7909Methyl Isobutyl KetoneSolvent

Conditions

Temperature
60 °C

Procedure

Water (47 cc.) and pyridine (16.1 cc.) are added to the sodium salt of 3-acetoxymethyl-2-carboxy-7-[(5,6-dihydro-1,4-dithiin-2-yl )acetamido]-8-oxo-5-thia-1-aza- bicyclo[4,2,0]oct-2-ene (45.2 g.) and potassium thiocyanate (194 g.). After stirring, a homogeneous syrupy mixture is obtained, the pH of which is adjusted to 6.5 by addition of concentrated phosphoric acid. The mixture is heated at 60° C. for 5 hours. After cooling, the reaction mixture is diluted with distilled water (1 liter) and is washed three times with chloroform (total 800 cc.). The last traces of chloroform in the aqueous phase are removed by distillation under reduced pressure (20 mm.Hg) and the resulting solution is then treated with decolourizing charcoal, filtered through "Supercel" and cooled by means of an ice-water bath. The solution is then acidified to pH 2 by addition of 4 N hydrochloric acid whilst keeping the temperature below 5° C.; a product precipitates. The mixture is stirred for one hour whilst continuing to cool it with a mixture of ice and water, and is then washed twice by decantation with ice-water (1 liter). The precipitate is filtered off and is washed three times with ice-water (total 2 liters). The solid obtained is suspended in water (120 cc.) and a 25% solution of "Amberlite LA 2" in methyl isobutyl ketone (120 cc.) is added. The mixture is stirred until the solid has dissolved completely, and then the organic phase is decanted and discarded. The aqueous phase is extracted twice with a 25% solution of "Amberlite LA 2" in methyl isobutyl ketone (total 240 cc.), then with ethyl acetate (300 cc.) and finally three times with diethyl ether (total 300 cc.). The water is evaporated under reduced pressure (20 mm.Hg) at 40° C. An oil is obtained which is triturated in acetone (800 cc.). The resulting solid is filtered off, washed three times with acetone (total 300 cc.) and then dried under reduced pressure (0.5 mm.Hg). 2-Carboxylato-7-[(5,6-dihydro-1,4-dithiin-2-yl )acetamido]-8-oxo-3- (1-pyridinio-methyl)-5-thia-1-aza-bicyclo[4,2,0]- oct-2-ene (8.3 g.) is thus obtained.

Workup

  1. customa homogeneous syrupy mixture is obtained
  2. temperatureAfter cooling
  3. washis washed three times with chloroform (total 800 cc.)
  4. customThe last traces of chloroform in the aqueous phase are removed by distillation under reduced pressure (20 mm.Hg)
  5. additionthe resulting solution is then treated with decolourizing charcoal
  6. filtrationfiltered through "Supercel"
  7. temperaturecooled by means of an ice-water bath
  8. additionThe solution is then acidified to pH 2 by addition of 4 N hydrochloric acid
  9. customthe temperature below 5° C.
  10. customa product precipitates
  11. stirringThe mixture is stirred for one hour
  12. temperatureto cool it
  13. additionwith a mixture of ice and water
  14. washis then washed twice by decantation with ice-water (1 liter)
  15. filtrationThe precipitate is filtered off
  16. washis washed three times with ice-water (total 2 liters)
  17. customThe solid obtained
  18. stirringThe mixture is stirred until the solid
  19. dissolutionhas dissolved completely
  20. customthe organic phase is decanted
  21. extractionThe aqueous phase is extracted twice with a 25% solution of "Amberlite LA 2" in methyl isobutyl ketone (total 240 cc.)
  22. customThe water is evaporated under reduced pressure (20 mm.Hg) at 40° C
  23. customAn oil is obtained which
  24. customis triturated in acetone (800 cc.)
  25. filtrationThe resulting solid is filtered off
  26. washwashed three times with acetone (total 300 cc.)
  27. customdried under reduced pressure (0.5 mm.Hg)

Sources & evidence

ORD record
ord-9a8e81d835f04b05876c430f45b4a2e3
Source dataset
uspto-grants-1977_02
Patent number
US04007176

Reaction notes

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