Formaldehyde → HCID 22406813, compound

HRID 440507Notes

Reaction equation

HRID 440507 reaction equation
[ClH:1].C[O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14]C)[CH:10]([C:16]1([C:20]3[CH:25]=[CH:24][C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:22][CH:21]=3)[CH2:19][CH2:18][CH2:17]1)[NH:9][CH2:8][CH2:7]2.C=O.[C:34]([BH3-])#N.[Na+]>CO>[ClH:1].[OH:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[OH:14])[CH:10]([C:16]1([C:20]3[CH:21]=[CH:22][C:23]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)=[CH:24][CH:25]=3)[CH2:17][CH2:18][CH2:19]1)[N:9]([CH3:34])[CH2:8][CH2:7]2

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 22406750HCID 22406750, compound

Product 1

HCID 22406813HCID 22406813, compoundYield 32.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 6,7-dimethoxy-1-[1-(4-biphenylyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride (3.5 g, prepared as described in Example RC20), methanol (50 ml), 37% aqueous formaldehyde solution (5 ml) and sodium cyanoborohydride (2.08 g) was stirred at ambient temperature for 24 hours. The solvents were removed in vacuo and the residue was partitioned between aqueous sodium hydroxide solution and ether. The ether extracts were dried over magnesium sulphate, the solution was filtered and the solvent removed in vacuo. The residue was dissolved in glacial acetic acid (30 ml). 48% Aqueous hydrobromic acid (30 ml) was added, and the mixture was heated under reflux under nitrogen for 6 hours. The solvents were removed in vacuo and the residue was recrystallised from methanol to give a solid which was partitioned between concentrated aqueous ammonia solution and ether. The ether extracts were washed with brine, dried and filtered. Dry hydrogen chloride was bubbled through the filtrate to yield 6,7-dihydroxy-2-methyl-1-[1-(4-biphenylyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride (1.1 g), m.p. 131°-135° C. (dec).

Workup

  1. customThe solvents were removed in vacuo
  2. customthe residue was partitioned between aqueous sodium hydroxide solution and ether
  3. dry with materialThe ether extracts were dried over magnesium sulphate
  4. filtrationthe solution was filtered
  5. customthe solvent removed in vacuo
  6. dissolutionThe residue was dissolved in glacial acetic acid (30 ml)
  7. addition48% Aqueous hydrobromic acid (30 ml) was added
  8. temperaturethe mixture was heated
  9. temperatureunder reflux under nitrogen for 6 hours
  10. customThe solvents were removed in vacuo
  11. customthe residue was recrystallised from methanol
  12. customto give a solid which
  13. customwas partitioned between concentrated aqueous ammonia solution and ether
  14. washThe ether extracts were washed with brine
  15. customdried
  16. filtrationfiltered
  17. customDry hydrogen chloride was bubbled through the filtrate

Sources & evidence

ORD record
ord-827b64969b17429db804de543503d7b1
Source dataset
uspto-grants-1996_05
Patent number
US05519034

Reaction notes

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