4-Methylmorpholine → Ethyl 1-(pyridin-4-yl)piperidine-4-carboxylate

HRID 1459429Notes

Reaction equation

HRID 1459429 reaction equation
[NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.Cl.Cl[C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1.CN1CCOCC1>CN1CCCC1>[N:17]1[CH:18]=[CH:19][C:14]([N:1]2[CH2:2][CH2:3][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:10][CH2:11]2)=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 70770Ethyl 4-piperidinecarboxylateHCID 818524-Chloropyridine hydrochloride

Product 1

HCID 9899468Ethyl 1-(pyridin-4-yl)piperidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 84541-MethylpyrrolidineSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl isonipecotate (6.0 g 38.66 mmol), 4-chloropyridine hydrochloride (5.9 g, 38.66 mmol) and N-methylmorpholine (9.3 g mL, 85.00 mmol), were dissolved in N-methylpyrrolidine (50 mL) and the resulting solution was heated at 100° C. for 48 h. The solution was concentrated in vacuo and the residue was dissolved in EtOAc and washed with water and brine (2×100 mL), then dried (Na2SO4) and evaporated. The resulting residue was purified by flash chromatography (5% MeOH/CHCl3) to afford 33-1 as a crystalline solid. 1H NMR (CDCl3) δ 8.21 (d, J=6.8 Hz, 2H), 6.78 (d, J=6.8 Hz, 2H), 4.18 (q, J=7.0 Hz, 2H), 3.85 (m, 2H), 3.10 (m, 2H), 2.61 (m, 1H), 2.05 (m, 2H), 1.85 (m, 2H), 1.23 (t, J=7.0 Hz, 3H). ##STR164## 4-Pyridylpiperidin-4-ylcarboxylic acid (33-2)

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with water and brine (2×100 mL)
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe resulting residue was purified by flash chromatography (5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-45132f8fb7dd49c8898c384c69c8e691
Source dataset
uspto-grants-1998_12
Patent number
US05854245

Reaction notes

Loading…