2-(4-Chlorophenoxy)-2-methylpropanoyl chloride → Clofibric Acid

Participants

Reaction Conditions

Reaction Steps

A mixture of [1S-[1α(4R*,6R*),2α,6β,8β,8aα]]-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-6-[2-(1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthalenyl)ethyl]tetrahydro-2H-pyran-2-one in an amount of 1.00 g (2.29 mmol), 18.6 ml of dry pyridine, 1.40 g (1.15 mmol) 4-N,N-dimethylaminopyridine and 5.34 g (22.9 mmol) of 2-(4-chlorophenoxy)-2-methylpropionyl chloride was heated at 50° C. for 63/4hour, then stirred overnight at room temperature. Ice chips were then added, and after 30 min the mixture was poured into ice water and extracted four times with diethylether. The combined ether layers were washed with water, then washed with 0.1M H2SO4 and then dried over a conventional drying agent, preferably anhydrous sodium sulfate. The mixture was filtered and volatiles removed under reduced pressure (i.e. below atmospheric pressure, preferably around 30 mm). The residue was dissolved in diethylether, washed with saturated sodium bicarbonate solution and dried over anhydrous sodium sulfate. The mixture was filtered and volatiles removed under reduced pressure to leave 1.6 of 2-(4-chlorophenoxy)-2-methylpropionic acid-[1S-[1α,3α,7β,8β(2R*,4R*),8aβ]]-8-[2[tetrahydro-4-[ [(1,1-dimethylethyl)dimethylsilyl]oxy]6-oxo-2H-pyran-2-yl]ethyl]-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-1-naphthalenyl ester as a brown oil which was used directly without further purification.

Provenance & Evidence