Tetrahydrofuran → (S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol

Participants

Reaction Steps

To a suspension of (R)-(+)-methyl p-tolylsulfoxide (1.00 g, 6.48 mmol) in 10 mL, of anhydrous THF at −78° C. was added LDA mono(tetrahydrofuran), 1.5 M solution in cyclohexane (4.32 mL, 6.48 mmol) over 5 minutes. The resulting clear yellow solution was stirred for an additional 15 minutes. 4-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one (1.81 g, 5.90 mmol) was then added via cannula with the aid of 4 mL of THF over 5 minutes. After 1 hour at −78° C., the reaction mixture was quenched with 50 mL of water and extracted with three 50 mL portions of EtOAc. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with 15%-25% EtOAc-hexanes) afforded sequentially (S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (1.49 g, 55%) and (R)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (670 mg, 25%). The diastereomeric excess was determined to be >99% for both isomers (HPLC peak area).

Provenance & Evidence