2-Aminopyridine → Tert-butyl 4-(imidazo[1,2-a]pyridin-3-yl)piperidine-1-carboxylate

HRID 1245565Notes

Reaction equation

HRID 1245565 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15](Br)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]3=[N:18][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 104392-AminopyridineHCID 184611401-t-Butyloxycarbonyl-4-(1-bromo-formylmethyl)piperidine

Product 1

HCID 21912736Tert-butyl 4-(imidazo[1,2-a]pyridin-3-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1.15 g of 1-tert-butoxycarbonyl-4-(1-bromo-formylmethyl)piperidine (from Step C) in 15 mL ethanol was added 388 mg of 2-aminopyridine. After refluxing for 18 h, the solvent was evaporated. The mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution. Aqueous layer was extracted with ethyl acetate (3×). The combined organic phase was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography with 50% ethyl acetate in hexanes, followed by 100% ethyl acetate to give the title compound as a solid. 1H NMR (500 MHz, CDCl3) δ 1.48 (s, 9H), 1.70 (m, 2H), 2.06 (d, J=13 Hz, 2H), 2.93–3.02 (m, 3H), 4.26 (br, 2H), 6.87 (t, J=6.8 Hz, 1H). 7.21(m, 1H), 7.44(s, 1H), 7.69(d, J=9.2 Hz,1H), 7.99 (d, J=6.9 Hz, 1H).

Workup

  1. temperatureAfter refluxing for 18 h
  2. customthe solvent was evaporated
  3. customThe mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution
  4. extractionAqueous layer was extracted with ethyl acetate (3×)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography with 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3ab3711f5c974c05b5ea32ccd6339f57
Source dataset
uspto-grants-2006_10
Patent number
US07125887B2

Reaction notes

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