Diisopropyl Ether → (4-(2,2-Dimethyl-1,3-dioxan-5-yl)methoxy-3,5-dimethylpyridin-2-yl)methanol monohydrate

Participants

Reaction Conditions

Reaction Steps

Acetic anhydride (1.10 kg) was added dropwise over 1.5 hours to a mixture heated to 50 to 60° C. of 4-(2,2-dimethyl-1,3-dioxan-5-yl)methoxy-2,3,5-trimethylpyridine 1-oxide (1.20 kg) and sodium acetate (0.18 kg). After 0.5 hours had passed, the mixture was heated for 4.5 hours at 80° C. The mixture was then cooled so that its internal temperature was not greater than 30° C., and left to stand. The mixture was then concentrated under reduced pressure. The resulting residue was dissolved in methanol (1.0 L), and the resultant solution was then charged over 1 hour into a mixture of 48% aqueous sodium hydroxide (0.71 kg) and chilled water (2.85 L). The solution was stirred at room temperature for 5 hours and 45 minutes, and then concentrated under reduced pressure. The concentrated residue was charged with water (3.0 L), and the resultant mixture was extracted with toluene (2.3 L×4). The combined toluene layers were washed with water (1.2 L). The resultant organic layer was filtered with Celite and then concentrated. The resulting residue was charged with diisopropyl ether (1.15 L) at room temperature, and this solution was further charged with warm water (45° C., 74 mL). Once crystal precipitation had been confirmed, the solution was stirred for 1 hour at 25° C. and then charged with heptane (3.6 L). The stirring was continued overnight. After stirring for a further 5 hours under ice cooling, the solution was filtered to obtain yellow crystals. The obtained yellow crystals were charged with diisopropyl ether (3.5 L) and dissolved at 50° C. Insoluble matter was removed by filtration, and the solution was then slowly cooled and allowed to age overnight at 5° C. The obtained crystals were filtered, washed with heptane (0.5 L) and wind-dried to obtain 0.69 kg of the title compound.

Provenance & Evidence