Sulfuric acid magnesium salt (1:1) → 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde

HRID 272864Notes

Reaction equation

HRID 272864 reaction equation
[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[N:12]1([CH2:17][CH2:18][CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3([CH2:33][OH:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[CH:23][CH:22]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1.S([O-])([O-])(=O)=O.[Mg+2]>ClCCl>[N:12]1([CH2:17][CH2:18][CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3([CH:33]=[O:34])[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)=[CH:23][CH:22]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 59837459{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methanolHCID 178418287HCID 178418287, compound

Product 1

HCID 598374274-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehydeYield 50.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Pyridinium chlorochromate (20.3 g, 0.09415 mol), 1.69 wt) was charged to a stirred suspension of celite (24 g, 2 wt) and {4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methanol (12.03 g, 0.03766 mol) in dichloromethane (120 ml, 10 vol) with stirring. The mixture was stirred at 18-25° C. for 3.5 hours after which time LC analysis showed the reaction to be 70% complete. Magnesium sulphate (12 g, 1 wt) was added and the resulting slurry filtered through a pad of aluminium oxide (activated, basic, Brockmann I, standard grade, ˜150 mesh) (481 g, 40 wt) eluting with 1% methanol/dichloromethane. Clean fractions were combined and evaporated to dryness at 40° C. The resulting brown solid was stirred in tertbutylmethylether (120 ml, 10 vol). Undissolved residue was removed by filtration and rinsed with tertbutylmethylether (3×120 ml, 3×10 vol). The combined filtrates were evaporated at 40° C. to yield 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (6.0 g, 50.2%) as a beige waxy solid.

Workup

  1. stirringThe mixture was stirred at 18-25° C. for 3.5 hours after which time LC analysis
  2. customthe reaction
  3. filtrationthe resulting slurry filtered through a pad of aluminium oxide (activated, basic, Brockmann I, standard grade, ˜150 mesh) (481 g, 40 wt)
  4. washeluting with 1% methanol/dichloromethane
  5. customevaporated to dryness at 40° C
  6. stirringThe resulting brown solid was stirred in tertbutylmethylether (120 ml, 10 vol)
  7. customUndissolved residue was removed by filtration
  8. washrinsed with tertbutylmethylether (3×120 ml, 3×10 vol)
  9. customThe combined filtrates were evaporated at 40° C.

Sources & evidence

ORD record
ord-f80e5e9ad73a4aeb93feea1e5d49c8aa
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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