Hydrochloric Acid → HCID 66936525, compound

HRID 1366686Notes

Reaction equation

HRID 1366686 reaction equation
[C:1]1([CH2:7][N:8](CC2C=CC=CC=2)[CH2:9][C@@H:10]([NH:12][C@H:13]([C:15]([O:17][CH3:18])=[O:16])[CH3:14])[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl>[Pd].CCO>[CH3:11][C@H:10]([NH:12][C@H:13]([C:15]([O:17][CH3:18])=[O:16])[CH3:14])[CH2:9][NH:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 15200592HCID 15200592, compound

Product 1

HCID 66936525HCID 66936525, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of methyl N-{(1S)-2-[bis(phenylmethyl)amino]-1-methylethyl}-L-alaninate (J. Org. Chem. 1995, 60, 4177-4183) (2.156 g, 6.33 mmol), concentrated hydrochloric acid 37% (0.805 mL), 5% palladium on carbon (0.863 g), and EtOH (40 mL) was hydrogenated under a hydrogen balloon for 48 h. The mixture was filtered through Celite, and the solids were washed with MeOH and CH2Cl2. The filtrates were combined and concentrated under reduced pressure. The residue was redissolved in EtOH (55 mL), p-toluenesulfonic acid (0.344 g) was added, and the mixture was heated at reflux for 16 h. The mixture was concentrated under reduced pressure and partitioned between CH2Cl2 and NaHCO3. The aqueous layer was back extracted with CH2Cl2, and the combined organic layers were dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (9:1, CH2Cl2:MeOH) to provide methyl N-{(1S)-1-methyl-2-[(phenylmethyl)amino]ethyl}-L-alaninate (685 mg, 50%). LCMS: (M+H)+: 129.1. The leftover aqueous layer was extracted further with 40% isopropanol in CHCl3 twice, and the combined organic layers were dried (Na2SO4), filtered, and concentrated to yield (3S,5S)-3,5-dimethyl-2-piperazinone (306 mg, 38%). LCMS: (M+H)+: 129.1.

Workup

  1. customfor 48 h
  2. filtrationThe mixture was filtered through Celite
  3. washthe solids were washed with MeOH and CH2Cl2
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was redissolved in EtOH (55 mL)
  6. additionp-toluenesulfonic acid (0.344 g) was added
  7. temperaturethe mixture was heated
  8. temperatureat reflux for 16 h
  9. concentrationThe mixture was concentrated under reduced pressure
  10. custompartitioned between CH2Cl2 and NaHCO3
  11. extractionThe aqueous layer was back extracted with CH2Cl2
  12. dry with materialthe combined organic layers were dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by flash chromatography (9:1, CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-16a9eb1f06334302b716800b8832feb9
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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