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

HRID 1178755Notes

Reaction equation

HRID 1178755 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 79.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

1-tert-Butoxycarbonyl-4-piperidone (6.87 g, 0.0345 mol, 1.15 eq) and 4-hydroxypiperidine (3.03 g, 0.03 mol, 1 eq) were stirred at room temperature in ethanol (25 ml) and acetic acid (2 ml) for 2 hours. To the solution was added 0.3 g of 5% palladium on carbon type 5214 Engelhard catalyst. The reaction was then hydrogenated under a pressure of 3.5 bar at room temperature for 24 hours. Further catalyst (0.3 g) was added and the reaction hydrogenated under a pressure of 3.5 bar for a further 19 hours. The catalyst was filtered off through CELITE™, washed with ethanol (10 ml) and evaporated in vacuo to an oil. To the oil was added 20% citric acid (10 ml) and isopropyl acetate (20 ml). The aqueous was collected and basified (10M aqueous sodium hydroxide, 3 ml) and the aqueous washed twice with MTBE (2×25 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 (6.9 g, 79.8% yield; 96.3% purity HPLC area %).

Workup

  1. customthe reaction hydrogenated under a pressure of 3.5 bar for a further 19 hours
  2. filtrationThe catalyst was filtered off through CELITE™
  3. washwashed with ethanol (10 ml)
  4. customevaporated in vacuo to an oil
  5. additionTo the oil was added 20% citric acid (10 ml) and isopropyl acetate (20 ml)
  6. customThe aqueous was collected
  7. washthe aqueous washed twice with MTBE (2×25 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-7635c74f8de74838acf82cdd4842210c
Source dataset
uspto-grants-2007_10
Patent number
US07276609B2

Reaction notes

Loading…