Morpholine → HCID 86710851, compound

HRID 406285Notes

Reaction equation

HRID 406285 reaction equation
[H-].[H-].COCCO[Al+]OCCOC.[Na+].N1CCOCC1.[CH3:21][O:22][CH2:23][O:24][CH2:25][C:26]1[N:31]2[CH:32]=[CH:33][N:34]=[C:30]2[C:29]([C:35](OC)=[O:36])=[CH:28][CH:27]=1>C1(C)C=CC=CC=1>[CH3:21][O:22][CH2:23][O:24][CH2:25][C:26]1[N:31]2[CH:32]=[CH:33][N:34]=[C:30]2[C:29]([CH:35]=[O:36])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 86710849Methyl 5-({[(methyloxy)methyl]oxy}methyl)imidazo[1,2-a]pyridine-8-carboxylate2×

Product 1

HCID 86710851HCID 86710851, compoundYield 56.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a stirred solution of sodium bis(2-methoxyethoxy)aluminium dihydride (65% wt. in toluene, 0.512 mL, 1.678 mmol) at 0° C. under a nitrogen atmosphere was added a solution of morpholine (0.147 mL, 1.678 mmol) in toluene (3.35 mL) dropwise over 15 min to give a solution of reducing agent (approx 4 mL, 4 eq). An aliquot of this solution (1.5 mL, ca 1.5 eq) was added dropwise over 2 min to a stirred solution of impure methyl 5-({[(methyloxy)methyl]oxy}methyl)imidazo[1,2-a]pyridine-8-carboxylate (105 mg, 0.420 mmol) in toluene (4 mL) at −40° C. The reaction was stirred at −40° C. for 40 min when LCMS indicated that the ester had been reduced to the aldehyde. The reaction was quenched carefully by addition of water (2 mL) and then allowed to warm to ambient temperature and concentrated in vacuo. The residue was pre-absorbed on florosil (100-200 mesh) and purified on a silica cartridge (20 g) using a 0-25% methanol-DCM gradient over 40 min. The appropriate fractions were combined and concentrated in vacuo to give impure 5-({[(methyloxy)methyl]oxy}methyl)imidazo[1,2-a]pyridine-8-carbaldehyde as a yellow oil (52 mg) which was used directly in the next step.

Workup

  1. customto give a solution
  2. customThe reaction was quenched carefully by addition of water (2 mL)
  3. temperatureto warm to ambient temperature
  4. concentrationconcentrated in vacuo
  5. customThe residue was pre-absorbed on florosil (100-200 mesh)
  6. custompurified on a silica cartridge (20 g)
  7. customover 40 min
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3265bb29e1d347bc98db4e6e2d06a39f
Source dataset
uspto-grants-2014_06
Patent number
US08754101B2

Reaction notes

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