Methanesulfonic Acid → (3R,4S,5S,6R)-2-(3-(4-((tert-butyldimethylsilyl)oxy)benzyl)-4-chlorophenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Participants

Reaction Conditions

Reaction Steps

A solution of (4-(2-chloro-5-iodobenzyl)phenyloxy)tert-butyldimethylsilane (10.0 g, 21.8 mmol) in anhydrous tetrahydrofuran (80 mL) and toluene (80 mL) was cooled to −78° C. To the solution was slowly added dropwise a solution of n-butyl lithium in n-hexane (2.4 mol/L, 13.6 mL, 32.6 mmol). The resulting mixture was reacted at −78° C. for 2 hr, and then warmed up to −60° C. To the reaction mixture was added a solution of (3R,4S,5R,6R)-3,4,5-tri((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetra hydro-2H-pyran-2-one (15.3 g, 32.7 mmol) in toluene (60 mL) in one batch. The resulting mixture was reacted at −60° C. for 2 hr. To the reaction mixture was added dropwise a solution of methanesulfonic acid (14.6 g, 152.1 mmol) in methanol (50 mL). After the completion of dropwise addition, the resulting mixture was reacted under stirring at room temperature for 17 hr. The reaction mixture was quenched with a saturated sodium bicarbonate solution, and separated into an aqueous phase and an organic phase. The aqueous phase was extracted with ethyl acetate (200 mL×3). The organic phases were combined, washed with a saturated sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under a reduced pressure to produce 9.0 g of a crude product, which was directly used in the next reaction without purification.

Provenance & Evidence