Methanol, magnesium salt (2:1) → HCID 49800017, compound

Participants

Reaction Steps

A stoichiometric amount of 7.6 wt.-% methanolic solution of magnesium methanolate (18.1 mL) was added to the solution of 9.0 g of esomeprazole (99.28% e.e.) in 100 mL of methanol. The obtained reaction mixture was stirred at room temperature for 1 hour allowing to form esomeprazole magnesium salt in the meantime. After addition of 0.4 mL of water the reaction mixture was further stirred for 30 min. The formed inorganic solid salts were separated from the liquid by filtration through a layer of diatomite filter medium (Celite®). The volume of filtrate was then reduced by evaporation of methanol forming an esomeprazole magnesium solution with concentration 40-45 wt.-%. A mixture of 51 mL of acetone and 2.9 mL of water was added to the concentrate. The mixture was seeded with a 0.05 g of esomeprazole magnesium dihydrate form B. After a few minutes a precipitate was formed and the suspension was stirred for 4 hours. The product was filtered off, washed twice with 10 mL of a mixture of acetone and methanol (4/1(V/V)). The wet filter cake was dried for 20 hours at reduced pressure (200 mbar). 8.00 g of esomeprazole magnesium dihydrate form B was obtained (99.84% e.e. determined by chiral HPLC, 100% purity determined by HPLC, 6.1% of water content determined by Karl-Fisher, 1.98% of residual solvents content (methanol, acetone) as determined by GC).

Provenance & Evidence