Triphenylphosphine → Triphenylphosphine Oxide

Participants

Reaction Conditions

Reaction Steps

To a well-stirred solution consisting of (7S,9aS)-cis-(2-Benzo[d]isoxazol-3-yl-octahydro-pyrido[1,2-a]pyrazin-7-yl)-methanol (3.40 g, 11.83 mmol), methyl-3-hydroxybenzoate (2.70 g, 17.75 mmol), and triphenylphosphine (3.70 g, 14.20 mmol), in anhydrous tetrahydrofuran (68 ml), diethylazodicarboxylate (2.24 ml, 14.20 mmol) was added. The resulting solution was heated at 50° C. for 2 hours. The solvent was removed in vacuo, and the resulting residue was extracted into a biphasic 1N aqueous sodium hydroxide (40 ml)/methylene chloride (50 ml) mixture. The aqueous phase was twice extracted with equal volume portions of fresh methylene chloride. The combined organic extracts were dried (anhydrous magnesium sulfate), and concentrated to an amber oil. An initial flash chromatography (silica gel, 70-230 micron mesh; elution with methanol/methylene chloride=1:99 in volume) afforded partially purified product (3.3 g, contaminants: hydrazine diethylcarboxylate and triphenylphosphine oxide). A second flash chromatography of the entire sample (silica gel, 230-400 micron mesh, elution with methanol/methylene chloride=1:99) afforded the purified title compound (1.37 g, 27% yield) as a colorless amorphous solid.

Provenance & Evidence