Acetic Acid → 3-(1-((Tert-butoxy)carbonyl)piperidin-4-yl)propanoic acid

HRID 1862536Notes

Reaction equation

HRID 1862536 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=[CH:8][C:9]([OH:11])=[O:10])=[CH:3][CH:2]=1.[C:12]([OH:15])(=[O:14])C>[Pd]>[C:4]([O:15][C:12]([N:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][C:9]([OH:11])=[O:10])[CH2:3][CH2:2]1)=[O:14])([CH3:7])([CH3:5])[CH3:3]

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 953033-(4-Pyridinyl)-2-propenoic acid

Product 1

HCID 15125403-(1-((Tert-butoxy)carbonyl)piperidin-4-yl)propanoic acid

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Conditions

Temperature
0 °C

Procedure

A mixture of 3-(4-pyridyl)-2-propenoic acid (10 g) , 10% Pd—C (1 g) in acetic acid (40 ml) was hydrogenated (3.0 kg/cm2) at 65° C. for 8 hours. After the catalyst was removed by filtration, the filtrate was concentrated in vacuo. The residue was resolved in toluene (30 ml) and concentrated in vacuo. The residue was resolved in water (30 ml) and tetrahydrofuran (50 ml), cooled to 0° C., and triethylamine (33 g) was added dropwise at 5° C. Di-t-butyl dicarbonate (18.3 g) was added to the mixture at 20° C. and stirred overnight. PH was adjusted to 7 with HCl, organic layer was washed with 10% aqueous citric acid (40 ml), 5% aqueous sodium chloride (40 ml), dried over magnesium sulfate (5 g) and concentrated in vacuo. The residue was resolved in toluene (20 ml), concentrated in vacuo to 25 ml. The mixture was stirred at 40° C. for 3 hours, n-heptane (20 ml) was added to the mixture and stirred at 0° C. overnight. The precipitate was separated and dried to give 3-(1-tert-butoxycarbonyl-4-piperidyl)propionic acid as white solid (12.8 g).

Workup

  1. customat 65° C.
  2. customfor 8 hours
  3. customAfter the catalyst was removed by filtration
  4. concentrationthe filtrate was concentrated in vacuo
  5. concentrationconcentrated in vacuo
  6. additiontriethylamine (33 g) was added dropwise at 5° C
  7. additionDi-t-butyl dicarbonate (18.3 g) was added to the mixture at 20° C.
  8. washwas washed with 10% aqueous citric acid (40 ml), 5% aqueous sodium chloride (40 ml)
  9. dry with materialdried over magnesium sulfate (5 g)
  10. concentrationconcentrated in vacuo
  11. concentrationconcentrated in vacuo to 25 ml
  12. stirringThe mixture was stirred at 40° C. for 3 hours
  13. additionn-heptane (20 ml) was added to the mixture
  14. stirringstirred at 0° C. overnight
  15. customThe precipitate was separated
  16. customdried

Sources & evidence

ORD record
ord-a7c03aaa0719489381c4b64ce3f97a31
Source dataset
uspto-grants-2003_03
Patent number
US06538007B1

Reaction notes

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