Potassium Hydroxide → Dihexyl ether

Participants

Reaction Steps

A mixture of 0.67 g (120 mmol) of powdered KOH in 20 ml of dry xylene was heated to reflux and ~10 ml of xylene was removed by distillation. To this stirred mixture was added a solution of 400 mg (1.49 mmol) of [1α,2β(Z),3β,4α]-7-[3-(hydroxymethyl)-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid, methyl ester prepared as described in U.S. Pat. No. 4,143,054 in 6 ml of xylene. Approximately 10 ml of xylene was removed by distillation to afford a clear solution with a gummy precipitate adhering to the magnetic stirring bar. To this mixture was added a solution of 1.45 g (7.5 mmol) of crude 2-methyl-hexylmesylate in 4 ml of xylene. This caused the gummy precipitate to break up to form a somewhat gelatinous reaction mixture. The mixture was refluxed for 21/4 hour. The cooled reaction mixture was partitioned between 20 ml each saturated NH4Cl and EtOAc. The aqueous layer was acidified to pH=3.5 and then extracted with three 20 ml portions of EtOAc. The combined EtOAc extracts were dried (MgSO4), filtered and concentrated in vacuo to give the crude product which was treated with excess ethereal CH2N2. The crude product was purified by flash chromatography on 35 g of silica gel using 4:1 hexane/ether as eluant. Fractions 15-20 were concentrated to give 320 mg of title ether (58%). Fractions 23-27 afforded 100 mg of the n-hexyl ether related to title ether (19%). (Apparently, the commercial 2-methyl-hexanoic acid which was the precursor to the mesylate employed was contaminated with ~10% hexanoic acid) and fractions 21-22 gave 70 mg (13%) of a mixture of these two ethers.

Provenance & Evidence