Hydrogen Bromide → 1,2,3,6-Tetrahydro-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-pyridinol

HRID 2304806Notes

Reaction equation

HRID 2304806 reaction equation
Br.[CH3:2][N:3]1[CH2:8][CH2:7][C:6](=O)[CH2:5][CH2:4]1.BrBr.[CH3:12][O:13][C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([O:22][CH3:23])[CH:15]=1.[OH-:24].[Na+]>C(O)(=O)C.O>[OH:24][CH:5]1[C:6]([C:15]2[C:16]([O:22][CH3:23])=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:14]=2[O:13][CH3:12])=[CH:7][CH2:8][N:3]([CH3:2])[CH2:4]1

Participants

8

Reactant 5

HCID 260Hydrogen Bromide2×HCID 14798Sodium HydroxideHCID 24408BromineHCID 693011,3,5-TrimethoxybenzeneHCID 740491-Methyl-4-piperidone

Product 1

HCID 99256571,2,3,6-Tetrahydro-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-pyridinol

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
25 °C

Procedure

75.7 ml (0.44 mol) of 33% strength HBr in glacial acetic acid were added to 100 ml of glacial acetic acid and 50 g (0.44 mol) of 1-methylpiperidin-4-one (III) were then vigorously added dropwise at 20-25 ° C. with ice-cooling. 70.4 g (0.44 mol) of bromine were added dropwise at 20-25° C. under nitrogen in the course of 30 min to the suspension of the hydrobromide obtained in this way, a clear, yellowish solution being obtained. This was stirred at 25° C. for a further 60 min and 67.2 g (0.40 mol) of 1,3,5-trimethoxybenzene (V) were then added to the reaction solution. It was then stirred at 25° C. for 1 h. After this, 400 ml of water were allowed to run in and the mixture was heated to reflux for 3 h. The reaction mixture was allowed to stand at room temperature overnight, diluted with 400 ml of water and then cooled to 10° C., and a total of 320 ml of conc. sodium hydroxide solution were added dropwise at this temperature in the course of 4 h to the well stirred mixture (pH after addition 10.7). In the course of this the allyl alcohol (VII) first precipitated in slightly oily form, but then on longer stirring became solid and could readily be filtered off with suction. The dark yellow precipitate was filtered off with suction, washed with water and dried well. The crude product was then stirred with 80 ml of acetone, filtered off with suction and dried in vacuo.

Workup

  1. additionwere then vigorously added dropwise at 20-25 ° C. with ice-
  2. temperaturecooling
  3. customobtained in this way
  4. customa clear, yellowish solution being obtained
  5. stirringIt was then stirred at 25° C. for 1 h
  6. temperaturewas heated
  7. temperatureto reflux for 3 h
  8. waitto stand at room temperature overnight
  9. temperaturecooled to 10° C.
  10. stirringstirred mixture (
  11. additionpH after addition 10.7)
  12. customIn the course of this the allyl alcohol (VII) first precipitated in slightly oily form
  13. stirringon longer stirring
  14. filtrationcould readily be filtered off with suction
  15. filtrationThe dark yellow precipitate was filtered off with suction
  16. washwashed with water
  17. customdried well
  18. stirringThe crude product was then stirred with 80 ml of acetone
  19. filtrationfiltered off with suction
  20. customdried in vacuo

Sources & evidence

ORD record
ord-509462e0fa1a49dba8190aea26259494
Source dataset
uspto-grants-2002_08
Patent number
US06437136B1

Reaction notes

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