2,3-Dihydroxybutanedioic Acid → HCID 18004026, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-(4-methylphenyl)-6-methylimidazo[1,2-a]-pyridine-3-acetic acid (59.2 g; 0.21 mols) in methylene chloride (820 mL) is added dropwise with oxalyl chloride (29.9 g; 0.23 mols) adjusting the addition according to the gas evolution and keeping the temperature below 35° C. The resulting suspension is added with 2-(4-methylphenyl)-6-methylimidazo[1,2-a]-pyridine-3-acetic acid (59.2 g; 0.21 mols) and oxalyl chloride (29.9 g; 0.23 mols) is added dropwise with the same procedure as in the previous step. The suspension is refluxed for 30 minutes, then cooled to 10÷15° C. and added with N,N-dimethylamine hydrochloride (98% titre, 41 g, 0.49 mols). Keeping the temperature below 15° C., triethylamine (167 g, 1.65 mols) is added dropwise. After one hour at room temperature, water is added (200 mL), the phases are separated and the lower organic phase is washed with a 5% sodium carbonate aqueous solution (200 mL) and subsequently with water (200 mL). The organic phase is concentrated to a residue, which is redissolved in methanol (1100 mL) under reflux, then added with natural tartaric acid (33.0 g, 0.22 mols). The resulting solution is slowly cooled to 0° C. and the precipitated solid is filtered under nitrogen and washed with cold methanol (2×50 mL). The humid solid is taken up in methanol (900 mL), refluxed until dissolution and added with active carbon (5 g). The hot clear solution is filtered, then slowly cooled to 0° C. and the precipitated solid is filtered under nitrogen, washed with cold methanol (2×50 mL) then dried at 50° C. under vacuum to yield Zolpidem tartrate (112.6 g, 100.8% titre, 99.85% HPLC purity, 70.1% yield).

Provenance & Evidence