Tetrahydrofuran → (S)-4-(5-bromo-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 (8.80 g, 57.0 mmol) in 100 mL of anhydrous THF at −78° C. was added LDA mono(tetrahydrofuran) 1.5 M solution in cyclohexane (38.0 mL, 57.0 mmol) over 20 minutes. The resulting clear yellow solution was stirred for an additional 15 minutes. 4-(5-bromo-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one (18.2 g, 51.9 mmol) dissolved in 40 mL of THF was then added by cannula over 15 minutes. After 1 hour at −78° C., the reaction mixture was quenched with 300 mL of water and extracted with three 300 mL portions of EtOAc. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution, then brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with 10%-25% EtOAc-hexanes) afforded sequentially (S)-4-(5-bromo-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (11.5 g, 44%) and (R)-4-(5-bromo-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (5.47 g, 21%). The diastereomeric excess was determined to be >99% for both isomers (HPLC peak area).

Provenance & Evidence