Hydrogen Bromide → HCID 10025404, compound

HRID 440504Notes

Reaction equation

HRID 440504 reaction equation
[BrH:1].C([O:9][C:10]1[CH:19]=[C:18]2[C:13]([CH2:14][CH2:15][NH:16][CH:17]2[C:20]2([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])[CH2:22][CH2:21]2)=[CH:12][C:11]=1[O:30][CH3:31])C1C=CC=CC=1.[CH2:32]=O.[Na].Cl.Br>CO>[BrH:1].[Cl:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:20]1([CH:17]2[C:18]3[C:13](=[CH:12][C:11]([O:30][CH3:31])=[C:10]([OH:9])[CH:19]=3)[CH2:14][CH2:15][N:16]2[CH3:32])[CH2:22][CH2:21]1

Participants

7

Reactant 5

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5360545SodiumHCID 22406703HCID 22406703, compound

Product 1

HCID 10025404HCID 10025404, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Conditions

Temperature
10 °C

Procedure

A mixture of 7-benzyloxy-1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-1,2,3,4-tetrahydroisoquinoline hydrobromide (5 g prepared as described in Example RC14), methanol (100 ml) and 37% aqueous formaldehyde solution (5 ml) was cooled to 10° C. Sodium borohyride (2.5 g) was added and the mixture stirred at ambient temperature for 2 hours. The methanol was evaporated in vacuo and the residue partitioned between dilute aqueous sodium hydroxide solution (100 ml) and ether (2×100 ml). The organic layer yielded an oil which was dissolved in methanol (25 ml) and concentrated hydrochloric acid (25 ml) and heated under reflux for 2 hours. The solvent was removed in vacuo and the residue dissolved in hot ethanol, decolorised, filtered and the solvent evaporated. The resulting solid was washed in ether, dried and then partitioned between ethyl acetate and concentrated aqueous ammonia solution. The organic layer yielded an oil which was dissolved in methanol. 48% Aqueous hydrobromic acid was added and the mixture heated under reflux for 2 hours. The solvents were removed by evaporation to yield a solid which was recrystallised from ethanol. The solid residue was washed with ether and dried in vacuo at 50° C. to give 1-[1-(2-chlorophenyl)cyclopropyl]-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrobromide, m.p. 150°-153° C. Yield 2.95 g.

Workup

  1. customThe methanol was evaporated in vacuo
  2. customthe residue partitioned between dilute aqueous sodium hydroxide solution (100 ml) and ether (2×100 ml)
  3. customThe organic layer yielded an oil which
  4. temperatureunder reflux for 2 hours
  5. customThe solvent was removed in vacuo
  6. dissolutionthe residue dissolved in hot ethanol
  7. filtrationfiltered
  8. customthe solvent evaporated
  9. washThe resulting solid was washed in ether
  10. customdried
  11. custompartitioned between ethyl acetate and concentrated aqueous ammonia solution
  12. customThe organic layer yielded an oil which
  13. temperaturethe mixture heated
  14. temperatureunder reflux for 2 hours
  15. customThe solvents were removed by evaporation
  16. customto yield a solid which
  17. customwas recrystallised from ethanol
  18. washThe solid residue was washed with ether
  19. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-c1cc6eba92c1488ab15510434cad69be
Source dataset
uspto-grants-1996_05
Patent number
US05519034

Reaction notes

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