p-Toluenesulfonic acid → HCID 131710398, compound

HRID 918441Notes

Reaction equation

HRID 918441 reaction equation
ClC(OCC)=O.CN1CCOCC1.COC(C=C([NH:21][C@H:22]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:23]([O-:25])=O)C)=O.[Na+].[CH3:33][C:34]1([CH3:46])[S:38][C@@H:37]2[C@H:39]([NH2:42])[C:40](=[O:41])[N:36]2[C@H:35]1[C:43]([OH:45])=[O:44].O.[C:48]1([CH3:58])[CH:53]=[CH:52][C:51]([S:54]([OH:57])(=[O:56])=[O:55])=[CH:50][CH:49]=1.[OH-].[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(=O)C.O>[CH3:33][C:34]1([CH3:46])[S:38][C@@H:37]2[C@H:39]([NH:42][C:23]([C@H:22]([NH2:21])[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[O:25])[C:40](=[O:41])[N:36]2[C@H:35]1[C:43]([OH:45])=[O:44].[C:48]1([CH3:58])[CH:49]=[CH:50][C:51]([S:54]([O-:57])(=[O:55])=[O:56])=[CH:52][CH:53]=1

Participants

10

Reactant 7

HCID 6101p-Toluenesulfonic acidHCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 110826-Aminopenicillanic acidHCID 14798Sodium HydroxideHCID 521998p-Toluenesulfonic acid monohydrateHCID 57347947HCID 57347947, compound

Product 1

HCID 131710398HCID 131710398, compoundYield 81.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7909Methyl Isobutyl KetoneSolvent2×

Procedure

Meanwhile, 4-methylpentan-2-one (70 ml) was stirred and cooled to 0° and ethyl chloroformate (2.0 ml, 0.0208 mole) and a 1% solution of N-methylmorpholine in 4-methylpentan-2-one (3 ml) were added. The solution was cooled to -5° and sodium (R)-N-(1-methoxycarbonylpropen-2-yl)-α-aminophenylacetate (5.42 g, 0.02 mole) was added. The suspension was stirred at 0° to -5° for 30 minutes and then cooled to -30°. The 6-APA solution prepared above was added so as to keep the temperature of the mixture between -25 and -30°. The mixture was stirred for 30 minutes at -30° when water (50 ml) was added. Aqueous 2.53 M toluene-p-sulphonic acid monohydrate solution (17 ml, 0.043 mole) together with 10 M aqueous sodium hydroxide solution (ca. 0.1 ml) were added to the stirred two-phase mixture to adjust the pH to and maintain it at 1.5. The mixture was stirred at 5° for 1 hour when more toluene-p-sulphonic acid solution was added to readjust the pH from 2.5 to 1.6. The resulting suspension was stirred for a further 2 hours at 5° and filtered. The wet cake was washed with 4-methylpentan-2-one (50 ml), sucked as dry as possible and washed by slurrying with ice-cold water (50 ml). The solid was refiltered, washed with ethyl acetate (20 ml) and dried in vacuo at 45° to give ampicillin toluene-p-sulphonate (8.51 g, 81.7% th.), [α]D25 + 173° (c 0.97; 0.2 M pH 7 phosphate buffer). We claim:

Workup

  1. temperaturecooled to 0°
  2. temperatureThe solution was cooled to -5°
  3. temperaturecooled to -30°
  4. additionabove was added so as
  5. customthe temperature of the mixture between -25 and -30°
  6. additionwas added
  7. temperaturemaintain it at 1.5
  8. additionwas added
  9. stirringThe resulting suspension was stirred for a further 2 hours at 5°
  10. filtrationfiltered
  11. washThe wet cake was washed with 4-methylpentan-2-one (50 ml)
  12. customas dry as possible and
  13. washwashed
  14. washwashed with ethyl acetate (20 ml)
  15. customdried in vacuo at 45°

Sources & evidence

ORD record
ord-8f946ca67af74d4c9292a5f1683556a8
Source dataset
uspto-grants-1976_07
Patent number
US03971775

Reaction notes

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