Acetic Acid → tert-Butyl 4-hydroxy-[1,4'-bipiperidine]-1'-carboxylate

HRID 1178754Notes

Reaction equation

HRID 1178754 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:15][CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(O)(=O)C>C(O)C.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:19]2[CH2:20][CH2:21][CH:16]([OH:15])[CH2:17][CH2:18]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 79341Piperidin-4-olHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 9835508tert-Butyl 4-hydroxy-[1,4'-bipiperidine]-1'-carboxylateYield 71.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

1-tert-Butoxycarbonyl-4-piperidone (4 g, 0.0201 mol, 1.3 eq) and 4-hydroxypiperidine (1.56 g, 0.054 mol, 1 eq) were stirred at room temperature in ethanol (20 ml) and acetic acid (2 ml) for 3 hours. To the solution was added 0.56 g of 5% palladium on carbon type 440 Johnson Matthey catalyst. The reaction was then hydrogenated under a pressure of 3 bar at room temperature for 16 hours. The catalyst was filtered off through CELITE™, washed with ethanol (40 ml) and evaporated in vacuo to an oil. The oil was dissolved in water (25 ml) and the aqueous washed twice with dichloromethane (2×20 ml). The aqueous was basified (5M aqueous sodium hydroxide, 12 ml) and the aqueous washed twice with dichloromethane (2×30 ml). The combined organics were dried (magnesium sulphate). The solution was filtered and evaporated in vacuo to give 4-(hydroxy)-[1,4′]bipiperidinyl-1′-carboxylic acid tert-butyl ester as a yellow oil (3.13 g, 71.5% yield, 95.4% purity HPLC area %).

Workup

  1. filtrationThe catalyst was filtered off through CELITE™
  2. washwashed with ethanol (40 ml)
  3. customevaporated in vacuo to an oil
  4. dissolutionThe oil was dissolved in water (25 ml)
  5. washthe aqueous washed twice with dichloromethane (2×20 ml)
  6. washthe aqueous washed twice with dichloromethane (2×30 ml)
  7. dry with materialThe combined organics were dried (magnesium sulphate)
  8. filtrationThe solution was filtered
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-05bad11f438b40f5a69279a722f01d60
Source dataset
uspto-grants-2007_10
Patent number
US07276609B2

Reaction notes

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