Methanesulfonic Acid → (3R,4S,5S,6R)-2-(2-(3-(but-2-ynyloxy)propyl)-4-chloro-5-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Participants

Reaction Steps

To a stirred −78° C. solution of 1-bromo-2-(3-(but-2-ynyloxy)propyl)-4-chloro-5-(4-ethoxybenzyl)benzene (BM) (0.2 g, 0.459 mmol) in 3 mL of 1:2 dry THF:toluene under Ar was added 0.22 mL of 2.5M n-BuLi in hexane (precooled to −78° C.) dropwise to insure the temperature remained below −70° C. After stirring for 40 min, the solution was transferred by cannula to a stirred −78° C. solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)-tetrahydropyran-2-one (0.279 g, 0.597 mmol) in 2.5 mL of toluene at a rate that maintained the reaction below −70° C. The mixture was stirred for 3 h at −78° C. prior to addition of MeSO3H (0.093 g, 0.964 mmol) in 2.5 mL of methanol below −75° C. After complete addition, the reaction solution was gradually warmed to room temperature and stirred overnight. After quenching by saturated aq. NaHCO3, the aqueous layer was extracted twice with EtOAc. The combined organic portions were washed with brine and dried over Na2SO4. After concentration, the residue was purified by preparative TLC (eluting with EtOAc:PE=1:5) to obtain 0.11 g of intermediate BN.

Provenance & Evidence