Hydrochloric Acid → HCID 13457936, compound

HRID 462737Notes

Reaction equation

HRID 462737 reaction equation
[CH3:1][N:2]1[CH2:22][CH2:21][N:5]2[CH2:6][C@@H:7]([C:14]3[CH:19]=[CH:18][C:17](N)=[CH:16][CH:15]=3)[C:8]3[C:13]([C@@H:4]2[CH2:3]1)=[CH:12][CH:11]=[CH:10][CH:9]=3.[N+]([O-])([O-])=O.[Na+].[ClH:28]>O>[ClH:28].[ClH:28].[CH3:1][N:2]1[CH2:22][CH2:21][N:5]2[CH2:6][C@@H:7]([C:14]3[CH:19]=[CH:18][C:17]([Cl:28])=[CH:16][CH:15]=3)[C:8]3[C:13]([C@@H:4]2[CH2:3]1)=[CH:12][CH:11]=[CH:10][CH:9]=3

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 24268Sodium NitrateHCID 13457934HCID 13457934, compound

Product 1

HCID 13457936HCID 13457936, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of cis-1,3,4,6,7,11b-hexahydro-2-methyl-7-(4-aminophenyl)-2H-pyrazino[2,1-a]isoquinoline (6.0 g, 0.0205 m) in conc HCl (40 ml) maintained under nitrogen at 0° was added dropwise a solution of sodium nitrate (1.55 g, 0.0225 m) in water (10 ml) over a period of 30 minutes. The mixture was stirred an additional 15 minutes, then added dropwise to a solution of cuprous chloride (4.0 g, 0.04 m) in conc HCl (20 ml) maintained at 0°. After the addition was complete, the ice bath was removed and the mixture allowed to warm to ambient temperature and stirred for 3 hours, during which time nitrogen evolution was observed. The mixture was heated briefly to 60° for 3 minutes, then cooled and poured onto 1000 cc of ice/water, and treated with chloroform (300 ml), then basified to pH 11 with 50% NaOH. The mixture was stirred for 15 minutes, then a jelly-like precipitate removed by filtration through glass wool. The filtrate was transferred to a separatory funnel and the layers separated, the aqueous phase extracted with chloroform (2×100 ml), and the combined chloroform extracts dried and evaporated to a yellow oil, 5.84 g. This material was purified by chromatography on a Prep 500 HPLC on silica gel, eluting with 1.5% ammoniated methanol/chloroform. The pure fractions were combined and evaporated to an oil, 2.82 g. This was dissolved in methanol (30 ml) and acidified with HCl gas. Upon standing, a solid crystallized and was collected by filtration and vacuum dried at 90° for 24 hours to give 2.31 g of cis-1,3,4,6,7,11b-hexahydro-2-methyl-7-(4-chlorophenyl)-2H-pyrazino[2,1-a]isoquinoline dihydrochloride, m.p. 274°-276°.

Workup

  1. temperaturemaintained at 0°
  2. additionAfter the addition
  3. customthe ice bath was removed
  4. stirringstirred for 3 hours, during which time nitrogen evolution
  5. temperatureThe mixture was heated briefly to 60° for 3 minutes
  6. temperaturecooled
  7. additionpoured onto 1000 cc of ice/water
  8. additiontreated with chloroform (300 ml)
  9. stirringThe mixture was stirred for 15 minutes
  10. customa jelly-like precipitate removed by filtration through glass wool
  11. customThe filtrate was transferred to a separatory funnel
  12. customthe layers separated
  13. extractionthe aqueous phase extracted with chloroform (2×100 ml)
  14. dry with materialthe combined chloroform extracts dried
  15. customevaporated to a yellow oil, 5.84 g
  16. customThis material was purified by chromatography on a Prep 500 HPLC on silica gel
  17. washeluting with 1.5% ammoniated methanol/chloroform
  18. customevaporated to an oil, 2.82 g
  19. dissolutionThis was dissolved in methanol (30 ml)
  20. customa solid crystallized
  21. filtrationwas collected by filtration and vacuum
  22. customdried at 90° for 24 hours

Sources & evidence

ORD record
ord-fbb9c48bdefa49bfb995d4460ce2be92
Source dataset
uspto-grants-1985_05
Patent number
US04517187

Reaction notes

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