Acetic Acid → 6-Methoxy-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine

HRID 1055171Notes

Reaction equation

HRID 1055171 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[N:5][C:6]2[N:11]=[CH:10]N[C:7]=2[CH:8]=1.[C:12](O)(=O)C>[Pd]>[CH3:1][O:2][CH:3]1[CH2:4][N:5]2[CH:12]=[CH:10][N:11]=[C:6]2[CH2:7][CH2:8]1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 668415106-methoxy-1H-imidazo[4,5-b]pyridine

Product 1

HCID 252095116-Methoxy-5,6,7,8-tetrahydroimidazo[1,2-a]pyridineYield 97%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

Add acetic acid (40 mL) to a heterogeneous solution of 6-methoxyimidazopyridine (1.0 g; 1.0 equiv; 6.75 mmoles) and 10% palladium on carbon (1.0 g; 1.4 equiv; 9.40 mmoles). Evacuate and backfill the reaction vessel with nitrogen (3×) then hydrogen (3×). Vigorously stir the reaction under hydrogen at ambient temperature for 3 hours. Filter the reaction mixture through celite, and wash the filter cake with a 1:1 mixture of dichloromethane and methanol. Concentrate the filtrate and dissolve the crude product mixture in 20 mL methanol, then load onto a scx ion-exchange column. Elute with methanol followed by 2M ammonia in methanol to give 6-methoxy-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (1.00 g; 97%) as a colorless oil. 1H NMR (DMSO): δ 1.84-1.94 (m, 1H), 2.00-2.09 (m, 1H), 2.63-2.68 (m, 2H), 3.27 (s, 3H), 3.77-3.82 (m, 1H), 3.92-4.03 (m, 2 H), 6.74 (d, 1H), 6.91 (d, 1H).

Workup

  1. customEvacuate
  2. customthe reaction under hydrogen at ambient temperature for 3 hours
  3. filtrationFilter the reaction mixture through celite
  4. washwash the filter cake
  5. additionwith a 1:1 mixture of dichloromethane and methanol
  6. concentrationConcentrate the filtrate
  7. dissolutiondissolve the crude product mixture in 20 mL methanol
  8. washElute with methanol

Sources & evidence

ORD record
ord-9e38de7be63d49698b30a10abeceb84f
Source dataset
uspto-grants-2016_07
Patent number
US09394317B2

Reaction notes

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