(R)-Methyl p-tolylsulfoxide → (S)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol

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Reaction Steps

To a suspension of (R)-(+)-methyl p-tolylsulfoxide (23.6 g, 153 mmol) in 200 mL of anhydrous THF at −78° C. was added lithium diisopropylamide mono(tetrahydrofuran) (LDA), 1.5 M solution in cyclohexane, 102 mL, 153 mmol) over 20 minutes. The resulting clear yellow solution was stirred for an additional 15 minutes. 1,1,1-Trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-one (36.4 g, 139 mmol) was then added via cannula with the aid of 125 mL of THF over 30 minutes. After 1.5 hours at −78° C., the reaction mixture was quenched with 600 mL of water and extracted with two 500 mL portions of ethyl acetate. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with 10%-30% EtOAc/hexanes) afforded sequentially (S)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (31.9 g, 55%, 99% de) and (R)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol.

Provenance & Evidence