2,3-Dihydroxybutanedioic Acid → HCID 18004026, compound

Temperature

15 °C

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).

1. additionthe addition
2. customthe temperature below 35° C
3. additionis added dropwise with the same procedure as in the previous step
4. temperatureThe suspension is refluxed for 30 minutes
5. additionis added dropwise
6. customthe phases are separated
7. washthe lower organic phase is washed with a 5% sodium carbonate aqueous solution (200 mL) and subsequently with water (200 mL)
8. concentrationThe organic phase is concentrated to a residue, which
9. dissolutionis redissolved in methanol (1100 mL)
10. temperatureunder reflux
11. temperatureThe resulting solution is slowly cooled to 0° C.
12. filtrationthe precipitated solid is filtered under nitrogen
13. washwashed with cold methanol (2×50 mL)
14. temperaturerefluxed until dissolution
15. additionadded with active carbon (5 g)
16. filtrationThe hot clear solution is filtered
17. temperatureslowly cooled to 0° C.
18. filtrationthe precipitated solid is filtered under nitrogen
19. washwashed with cold methanol (2×50 mL)
20. customthen dried at 50° C. under vacuum

ORD record

ord-b5fff6ff3b16445a93126a9c7de413da

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06384226B2