Hydrochloric Acid → HCID 69416431, compound

HRID 853066Notes

Reaction equation

HRID 853066 reaction equation
[Cl:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:15](=O)[NH:14][CH2:13][C@@H:12]([CH3:17])[N:6]3[C:7]=2[C:8]([F:11])=[CH:9][CH:10]=1.[Mg].Cl.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>CO.C(OCC)C.O>[ClH:1].[Cl:1][C:2]1[C:3]2[CH2:4][C@@H:5]3[CH2:15][NH:14][CH2:13][C@@H:12]([CH3:17])[N:6]3[C:7]=2[C:8]([F:11])=[CH:9][CH:10]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 5462224MagnesiumHCID 21226445Aluminium lithium hydrideHCID 69415538HCID 69415538, compound

Product 1

HCID 69416431HCID 69416431, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

(R)-9-Chloro-6-fluoro-4-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one 4.7 mmol) was dissolved in methanol and magnesium (0.69 g, 28.5 mmol) was added with stirring. Stirring was continued for 3 h at room temperature, the mixture was poured onto ice water and hydrochloric acid (1 N, 23 mL) was added. The pH was adjusted to neutral with potassium phosphate buffer (1 M, pH 6.85) and the mixture was extracted with ethyl acetate. Organic phase were pooled, washed with brine, dried with MgSO4 and the solvent was removed in vacuo to yield a mixture of (4R,10aR)- and (4R,10aS)-9-chloro-6-fluoro-4-methyl-3,4,10,10a-tetrahydro-2H-pyrazino[1,2-a]indol-1-one. Without further purification this mixture (1.2 g) was dissolved in diethylether (50 mL), lithium aluminium hydride (460 mg, 12.0 mmol) was added and the mixture was heated to reflux for 4 h. The solution was cooled and hydrolyzed by sequential addition of water (6.0 mL), sodium hydroxide solution (15%, 12.0 mL) and water (12.0 mL). Diethylether was added (300 mL), the mixture was filtered and the filtrate was evaporated after drying with MgSO4. Chromatography on silica gel (dichloromethane/methanol 97:3) separated the title compound (0.23 g; 20%) from the isomeric (4R,10aS)-9-chloro-6-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole. The title compound was characterized as its HCl salt which precipitated from diethylether, ISP-MS: m/e=241.3 (M+H+) and αD20=−18.4.

Workup

  1. stirringStirring
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried with MgSO4
  6. customthe solvent was removed in vacuo
  7. customto yield
  8. customWithout further purification this mixture (1.2 g)
  9. dissolutionwas dissolved in diethylether (50 mL)
  10. temperaturethe mixture was heated
  11. temperatureto reflux for 4 h
  12. temperatureThe solution was cooled
  13. filtrationthe mixture was filtered
  14. customthe filtrate was evaporated
  15. dry with materialafter drying with MgSO4
  16. customChromatography on silica gel (dichloromethane/methanol 97:3) separated the title compound (0.23 g; 20%) from the isomeric (4R,10aS)-9-chloro-6-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole
  17. customprecipitated from diethylether, ISP-MS

Sources & evidence

ORD record
ord-73ff52ead8664cf5a8fc3be4664fa410
Source dataset
uspto-grants-2007_08
Patent number
US07253281B2

Reaction notes

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