Hydrochloric Acid → (8aS)-4-benzhydryloctahydropyrrolo[1,2-a]pyrazine dihydrochloride

HRID 1006325Notes

Reaction equation

HRID 1006325 reaction equation
C(OC([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[CH2:16][N:17](CC1C=CC=CC=1OC)[CH2:18][C:19](=O)[CH:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=O)C1C=CC=CC=1.[ClH:43]>CO.[Pd]>[ClH:43].[ClH:43].[CH:20]([CH:19]1[N:11]2[CH2:15][CH2:14][CH2:13][C@H:12]2[CH2:16][NH:17][CH2:18]1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 69746794(2S)-2-[[N-(2-Oxo-3,3-diphenylpropyl)-(2-methoxybenzyl)amino]methyl]pyrrolidine-1-carboxylic acid benzyl ester

Product 1

HCID 69818813(8aS)-4-benzhydryloctahydropyrrolo[1,2-a]pyrazine dihydrochloride

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

(2S)-2-[[N-(2-Oxo-3,3-diphenylpropyl)-(2-methoxybenzyl)amino]methyl]pyrrolidine-1-carboxylic acid benzyl ester (492 mg) was dissolved in a mixture of methanol (7.4 ml) and IN hydrochloric acid (0.5 ml), and the solution was hydrogenated over 10% palladium—charcoal (50% wet) (0.15 g) at room temperature under atmospheric pressure for 15 hours. After removal of the catalyst by filtration, the filtrate was evaporated under reduced pressure. The residue was partitioned between aqueous saturated sodium hydrogen carbonate and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (4:1). The fractions containing the objective compound were collected and evaporated under reduced pressure and the resulting residue was treated with 4N hydrogen chloride in ethyl acetate to give (8aS)-4-benzhydryloctahydropyrrolo[1,2-a]pyrazine dihydrochloride (221.2 mg) as a colorless solid.

Workup

  1. customAfter removal of the catalyst
  2. filtrationby filtration
  3. customthe filtrate was evaporated under reduced pressure
  4. customThe residue was partitioned between aqueous saturated sodium hydrogen carbonate and ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (4:1)
  9. additionThe fractions containing the objective compound
  10. customwere collected
  11. customevaporated under reduced pressure
  12. additionthe resulting residue was treated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-b0a8cd1339a54d94a705dc3bf30328b6
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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