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

HRID 1178753Notes

Reaction equation

HRID 1178753 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 77%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

1-tert-Butoxycarbonyl-4-piperidone (3.94 g, 0.0198 mol, 1 eq) and 4-hydroxypiperidine (2 g, 0.0198 mol, 1 eq) were stirred at room temperature in ethanol (20 ml) and acetic acid (4 ml) for 3 hours. To the solution was added 0.6 g of 5% palladium on carbon type 38H Johnson Matthey catalyst The reaction was then hydrogenated under a pressure of 4 bar at room temperature for 68 hours. The catalyst was filtered off through CELITE™, washed with ethanol (60 ml) and evaporated in vacuo to an oil. To the oil was added 10% citric acid (7 ml), water (10 ml) and dichloromethane (40 ml). The aqueous was collected and basified (5M aqueous sodium hydroxide, 12 ml) and the aqueous washed twice with dichloromethane (2×30 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 (4.35 g, 77% yield; 90% purity HPLC area %).

Workup

  1. filtrationThe catalyst was filtered off through CELITE™
  2. washwashed with ethanol (60 ml)
  3. customevaporated in vacuo to an oil
  4. additionTo the oil was added 10% citric acid (7 ml), water (10 ml) and dichloromethane (40 ml)
  5. customThe aqueous was collected
  6. washthe aqueous washed twice with dichloromethane (2×30 ml)
  7. washThe combined organics were washed with brine
  8. dry with materialdried (magnesium sulphate)
  9. filtrationThe solution was filtered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-d5c7ee167b7f4ed08f3b411cf37e4f95
Source dataset
uspto-grants-2007_10
Patent number
US07276609B2

Reaction notes

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