(4-Carboxybutyl)triphenylphosphonium bromide → (Z)-7,7-dimethyl-8-[(tetrahydro-2H-pyran-2-yl)oxy]-5-octenoic acid

Participants

Reaction Steps

To a suspension of 4.43 g (10 mmols) of (4-carboxybutyl)triphenylphosphonium bromide in 20 ml of hexamethylphosphorictriamide and 28 ml of tetrahydrofuran was added dropwise at 0°-5° C., and under argon, 12 ml of 1.6 M butyllithium in hexane. The reaction mixture turned deep red in color. After stirring for 1 hr. at room temperature, 1.08 g (5.86 mmoles) of 2,2-dimethyl-3-[(tetrahydro-2H-pyran-2-yl)oxy]propanal (H. Marschall, et al., Chem. Ber. 107, 887 (1974)) in 3 ml of tetrahydrofuran was added. The resulting mixture was stirred for 17 hrs. at room temperature and then diluted with brine and extracted with hexane. The aqueous phase was acidified with a saturated solution of oxalic acid and extracted four times with ether. The ether extracts were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed in vacuo to yield 2.4 g of crude (Z)-7,7-dimethyl-8-[(tetrahydro-2H-pyran-2-yl)oxy]-5-octenoic acid which was subsequently converted into the methyl ester derivative by treatment with a freshly prepared ethereal solution of diazomethane. The crude ester (2.35 g), obtained after removal of the solvent, was chromatographed on a silica gel column. A mixture of hexane-ether (7:3) eluted 1.24 g (75.2%) of (Z)-7,7-dimethyl-8-[(tetrahydro-2H-pyran-2-yl)oxy]-5-octenoic acid methyl ester. This material was dissolved in 15 ml of methanol and treated with 0.5 ml of 2 N hydrochloric acid. The mixture was stirred for 3 hrs. at room temperature. Ca. 10 ml of methanol was evaporated in vacuo. The remaining solution was diluted with ether and poured into a saturated solution of sodium bicarbonate. The organic layer was washed with brine, dried (MgSO4), and concentrated under reduced pressure to yield 0.940 g of crude material. Chromatographic purification of the product on a silica gel column yielded 0.610 g (69.8%) of pure (Z)-8-Hydroxy-7,7-dimethyl-5-octenoic acid methyl ester (98.9% pure, by GC).

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