Hydrogen Bromide → HCID 22406776, compound

HRID 440492Notes

Reaction equation

HRID 440492 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][NH:15][CH:16]2[C:19]2([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])[CH2:22][CH2:21][CH2:20]2)=[CH:11][C:10]=1[O:30][CH3:31])C1C=CC=CC=1.C=O.[C:34]([BH3-])#N.[Na+].Cl.[BrH:39]>CO.CC(O)C>[BrH:39].[Cl:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:19]1([CH:16]2[C:17]3[C:12](=[CH:11][C:10]([O:30][CH3:31])=[C:9]([OH:8])[CH:18]=3)[CH2:13][CH2:14][N:15]2[CH3:34])[CH2:22][CH2:21][CH2:20]1

Participants

8

Reactant 5

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 22406908HCID 22406908, compound

Product 1

HCID 22406776HCID 22406776, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 3776IsopropanolSolvent

Conditions

Temperature
10 °C

Procedure

A mixture of the hydrochloride salt of 7-benzyloxy-1-[1-(2-chlorophenyl)cyclobutyl]-6-methoxy-1,2,3,4-tetrahydroisoquinoline (2.75 g prepared in a similar manner to that described in Example RB25), methanol (50 ml) and 37-40% aqueous formaldehyde solution (3 ml) was cooled to 10° C. and sodium cyanoborohydride (1.52 g) was added. The mixture was stirred for 24 hours and the solvents removed by evaporation. The residue was partitioned between ethyl acetate and dilute aqueous sodium hydroxide solution. The organic layer yielded a gum which was dissolved in methanol (25 ml) and concentrated hydrochloric acid (25 ml) and heated under reflux for 1 hour. The solvents were removed by evaporation and the residue partitioned between ether and saturated aqueous sodium bicarbonate solution. The ether layer yielded a residue which was dissolved in propan-2-ol (100 ml) and 48% aqueous hydrobromic acid (5 ml). The solvent was removed by evaporation and the residue crystallised and then recrystallised from propan-2-ol to give 1-[1-(2-chlorophenyl)cyclobutyl]-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrobromide, m.p. 148°-150° C.

Workup

  1. customprepared in a similar manner to that
  2. customthe solvents removed by evaporation
  3. customThe residue was partitioned between ethyl acetate and dilute aqueous sodium hydroxide solution
  4. customThe organic layer yielded a gum which
  5. temperatureunder reflux for 1 hour
  6. customThe solvents were removed by evaporation
  7. customthe residue partitioned between ether and saturated aqueous sodium bicarbonate solution
  8. customThe ether layer yielded a residue which
  9. customThe solvent was removed by evaporation
  10. customthe residue crystallised
  11. customrecrystallised from propan-2-ol

Sources & evidence

ORD record
ord-dd7549bd12774a3cb0e3b4a84ddb0bb8
Source dataset
uspto-grants-1996_05
Patent number
US05519034

Reaction notes

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