2-Chloropyridine → 2-(4-Boc-Aminopiperidino)pyridine

HRID 2421981Notes

Reaction equation

HRID 2421981 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]1.CCOC(C)=O>CS(C)=O>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:8]1[CH2:9][CH2:10][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:18])[CH3:20])[CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 79772-ChloropyridineHCID 8857Ethyl AcetateHCID 7238334-(N-Boc-amino)piperidine

Product 1

HCID 537924442-(4-Boc-Aminopiperidino)pyridineYield 27%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
140 °C

Procedure

A solution of 2-chloropyridine (0.83 ml, 8.81 mmol), tert-butyl piperidine-4-ylcarbamate (1.85 g, 9.24 mmol) and TEA (0.98 mL, 9.69 mmol) in DMSO (5 mL) was heated at 120° C. for 4 h 45 mins and then warmed to 140° C. for 2 days. EtOAc was added and the organic phase was washed with water then brine before evaporating to dryness. The residue was purified on a Biotage Horizion HPFC system eluting with 20% EtOAc in petroleum ether (40-60° C.) to give the title compound (0.65 mg, 27%). 1H NMR (500 MHz, CDCl3): 8.19 (s, 1H), 7.48 (dd, 1H), 6.67 (d, 1H), 6.61 (t, 1H), 4.49 (bs, 1H), 4.21 (d, 2H), 3.70 (bs, 1H), 2.99 (t, 2H), 2.05 (d, 2H), 1.59-1.38 (m, 11H). 13C NMR (CDCl3): 159.5, 155.4, 148.2, 137.7, 113.3, 107.5, 79.6, 48.4, 44.6, 32.3, 28.7; Mass Spectrum: M+H 278.

Workup

  1. washthe organic phase was washed with water
  2. custombrine before evaporating to dryness
  3. customThe residue was purified on a Biotage Horizion HPFC system
  4. washeluting with 20% EtOAc in petroleum ether (40-60° C.)

Sources & evidence

ORD record
ord-53a432aa69654e52a3d08d56f07c0a2e
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Reaction notes

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