Acetic Acid → (R)-1-(Piperidin-4-YL)ethanol

HRID 423634Notes

Reaction equation

HRID 423634 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C@H:7]([OH:9])[CH3:8])=[CH:3][CH:2]=1.C(O)(=O)C>CO.O=[Pt]=O>[NH:1]1[CH2:6][CH2:5][CH:4]([C@H:7]([OH:9])[CH3:8])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 11804747(1R)-1-(pyridin-4-yl)ethan-1-ol

Product 1

HCID 40614391(R)-1-(Piperidin-4-YL)ethanolYield 57%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 887MethanolSolvent

Procedure

A solution of (1R)-1-(4-pyridinyl)ethanol (37 g, 0.3 mol, 78% ee) in MeOH (2 L) was charged with PtO2 (5 g) under nitrogen atmosphere followed by acetic acid (19 mL). The mixture was evacuated and purged with hydrogen several times and then stirred under an atmosphere of hydrogen for 2 d at room temperature. The mixture was filtered to remove catalyst and the filtrate was concentrated in vacuo and triturated with EtOAc to yield a cream-colored solid which was collected by filtration. The filter cake was dissolved in MeOH (500 mL) and 50% NaOH (15.8 g) was added. The resulting solution was stirred at 25° C. for 30 min and concentrated. The resulting solid was triturated with Et2O (700 mL) and stirred at 25° C. for 30 min, the solids were removed by filtration and the filtrate was dried over MgSO4 and filtered again. The final filtrate was concentrated to yield (1R)-1-(4-piperidinyl)ethanol (22 g, 57% yield) as a light beige solid. 1H NMR (400 MHz, CDCl3): δ 3.50 (quint, 1H, J=6.3 Hz), 3.13-3.01 (m, 2H), 2.61-2.47 (m, 2H), 1.88 (br, 2H), 1.84-1.73 (m, 1H), 1.63-1.52 (m, 1H), 1.41-1.27 (m, 1H), 1.23-1.05 (m, 2H), 1.13 (d, 3H, J=6.2 Hz).

Workup

  1. customThe mixture was evacuated
  2. custompurged with hydrogen several times
  3. filtrationThe mixture was filtered
  4. customto remove catalyst
  5. concentrationthe filtrate was concentrated in vacuo
  6. customtriturated with EtOAc
  7. customto yield a cream-colored solid which
  8. filtrationwas collected by filtration
  9. dissolutionThe filter cake was dissolved in MeOH (500 mL)
  10. addition50% NaOH (15.8 g) was added
  11. stirringThe resulting solution was stirred at 25° C. for 30 min
  12. concentrationconcentrated
  13. customThe resulting solid was triturated with Et2O (700 mL)
  14. stirringstirred at 25° C. for 30 min
  15. customthe solids were removed by filtration
  16. dry with materialthe filtrate was dried over MgSO4
  17. filtrationfiltered again
  18. concentrationThe final filtrate was concentrated

Sources & evidence

ORD record
ord-e4f8b58f0c274328946ec335e5359b19
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

Loading…