Methanol → Tert-butyl Piperidine-4-carboxylate

HRID 524924Notes

Reaction equation

HRID 524924 reaction equation
O.[N:2]1(C(OCC2C=CC=CC=2)=O)[CH2:7][CH2:6][CH:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H][H].CO>CCOC(C)=O.[Pd]>[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 15126991-Benzyl 4-tert-butyl piperidine-1,4-dicarboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 1512676Tert-butyl Piperidine-4-carboxylateYield 91.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a 3 L florentine under nitrogen was charged Pd on C, wet, Degussa (10% Pd, 50% WATER) (8.120 g, 76.30 mmol) then EtOAc (1.706 L). The mixture was degassed via N2/vacuum cycles (3×), then a solution of O1-benzyl O4-tert-butyl piperidine-1,4-dicarboxylate 21 (243.7 g, 763.0 mmol) in EtOAc (243.7 mL) was added. Mixture was stirred under a hydrogen atmosphere overnight. Hydrogen was replenished and mixture was stirred for a further 3.5 h. Methanol (60 mL) was added to aid dissolution of precipitate then filtered through celite, washing through with methanol. Filtrate concentrated in vacuo to leave a brown oil with a slight suspension of a white solid, 138.6 g. Solid removed by filtration, and washed with minimal EtOAc. Filtrate was concentrated in vacuo to leave desired product as a light brown oil (129 g, 91%). 1H NMR (500 MHz, DMSO-d6) δ 2.88 (dt, 2H), 2.44 (td, 2H), 2.23 (tt, 1H), 1.69-1.64 (m, 2H) and 1.41-1.33 (m, 11H).

Workup

  1. customThe mixture was degassed via N2/vacuum cycles (3×)
  2. stirringmixture was stirred for a further 3.5 h
  3. dissolutiondissolution of precipitate
  4. filtrationthen filtered through celite
  5. washwashing through with methanol
  6. concentrationFiltrate concentrated in vacuo
  7. customto leave a brown oil
  8. additionwith a slight suspension of a white solid, 138.6 g
  9. customSolid removed by filtration
  10. washwashed with minimal EtOAc
  11. concentrationFiltrate was concentrated in vacuo

Sources & evidence

ORD record
ord-af4d3919579243ceb8cd8e113dee891a
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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