Water → (R)-3,4,4-Trimethoxytetrahydro-2H-pyran

Participants

Reaction Steps

A 12-L 4-neck round bottom flask equipped with a overhead air stirrer, addition funnel with nitrogen inlet adapter, condenser, and thermocouple was charged with (R)-4,4-dimethoxytetrahydro-2H-pyran-3-ol (as prepared in the previous step, 163 g, 1.0 mol) in THF (2.4 L) and stirred in ice/acetone bath until <0° C. KOtBu (113 g, 1.0 mol) was added in one portion, and after stirring 45 min, dimethyl sulfate (95 mL, 1.0 mol) was added via addition funnel over 15 min. The reaction was allowed to stir at room temperature for 2 h. The reaction mixture was poured into a reparatory flask containing H2O (1.2 L) and CH2Cl2 (1.2 L) and the layers were separated. The aqueous layer was back-extracted with CH2Cl2 (900 mL). The combined organic layers were washed with brine (1.0 L; Note: organic layer was on top), dried over MgSO4, filtered and evaporated to afford the title compound (177.1 g, 99%, chiral GC 94.4% ee) as a light yellow oil.

Provenance & Evidence