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

HRID 1178752Notes

Reaction equation

HRID 1178752 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 46%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

1-tert-Butoxycarbonyl-4-piperidone (4.02 g, 0.0217 mol, 1.3 eq) and 4-hydroxypiperidine (1.57 g, 0.0155 mol, 1 eq) were stirred at room temperature in ethanol (18 ml) and acetic acid (2 ml) for 10 minutes. To the solution was added 0.62 g of 5% palladium on carbon type 437 Johnson Matthey catalyst. The reaction was then hydrogenated under a pressure of between 4 and 4.5 bar at room temperature for 26 hours. The catalyst was filtered off through CELITE™, washed with ethanol (40 ml) and evaporated in vacuo to an oil. To the oil was added acetic acid (1 ml) and the oil partitioned between water (20 ml) and dichloromethane (30 ml). The aqueous was collected and basified (5M aqueous sodium hydroxide, 5 ml) and the aqueous washed twice with dichloromethane (2×20 ml). The combined organics were washed with brine and 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 (2.03 g, 46% yield; 92.1% 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. additionTo the oil was added acetic acid (1 ml)
  5. customthe oil partitioned between water (20 ml) and dichloromethane (30 ml)
  6. customThe aqueous was collected
  7. washthe aqueous washed twice with dichloromethane (2×20 ml)
  8. washThe combined organics were washed with brine
  9. dry with materialdried (magnesium sulphate)
  10. filtrationThe solution was filtered
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-73f41997dd6f452cb394667967d643d8
Source dataset
uspto-grants-2007_10
Patent number
US07276609B2

Reaction notes

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