Methanesulfonic Acid → (3R,4S,5S,6R)-2-(4-Chloro-3-(4-ethoxybenzyl)-5-methoxyphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Participants

Reaction Conditions

Reaction Steps

To a solution of bromide 74 (5.74 g, 16.14 mmol) in toluene/THF (72 mL/36 mL) at −78° C. under an atmosphere of nitrogen was added dropwise n-butyllithium (2.5M in hexane, 7.8 mL, 19.36 mmol), and the mixture was stirred for 40 min at the same temperature. Then a solution of TMS-protected gluconolactone 74-1 (9.04 g, 19.36 mmol) in toluene (30 mL) was added dropwise, and the mixture was stirred for 1 hour at the same temperature. To a solution of crude alcohol 74-2 were added CH3SO3H (0.6 N in MeOH, 53.8 mL, 32.28 mmol) at −78° C. The mixture was allowed to slowly warm to −40° C. To a mixture was added aq. saturated NaHCO3 solution (50 mL) to quench the reaction. After dilution with water, the mixture was stirred at room temperature for 30 min and extracted with EtOAc (100 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The (3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)-5-methoxyphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol 74-3 (6.6 g) was carried on to the next step without further purification.

Provenance & Evidence