反应详情

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.

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.