Reaktion #2270858

Reaktionsgleichung

3-(benzo[b]thiophen-4-yl)-2-methyl-5,6-dihydroimidazo[2,1-b]thiazole hydrochloride

sodium hydrogencarbonate

→

2-methyl-3-(2-methylbenzo[b]thiophen-4-yl)-5,6-dihydroimidazo[2,1-b]thiazole hydrochloride

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeprepared in a manner similar to
2. 2
   Extraktionthe free base was extracted into dichloromethane (2×50 ml)
3. 3
   TrocknenThe combined extracts were dried (MgSO4)
4. 4
   Sonstigethe solvent was removed in vacuo
5. 5
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (40 ml)
6. 6
   Temperaturthe stirred solution was cooled to −70° C.
7. 7
   workup.ADDITIONn-butyllithium (2.5M solution in hexanes; 2.85 ml) was added dropwise under nitrogen
8. 8
   workup.STIRRINGThe mixture was stirred at −70° C. for 1 hour
9. 9
   workup.ADDITIONmethyl iodide (0.45 ml) was added dropwise
10. 10
    workup.STIRRINGThe mixture was stirred at −70° C. for 1 hour
11. 11
    workup.ADDITIONit was poured into saturated aqueous ammonium chloride solution (50 ml)
12. 12
    ExtraktionThe product was extracted into ethyl acetate (2×50 ml)
13. 13
    Trocknenthe combined extracts were dried (MgSO4)
14. 14
    Sonstigethe solvents were removed in vacuo
15. 15
    SonstigeThe residue was purified via flash chromatography over silica using
16. 16
    workup.ADDITIONa 9:1 mixture of dichloromethane and methanol as eluant
17. 17
    Sonstigethe solvents were removed in vacuo
18. 18
    workup.DISSOLUTIONThe residue was dissolved in ethanol
19. 19
    workup.ADDITIONconcentrated hydrochloric acid (10 drops) was added
20. 20
    Sonstigethe solvent was removed in vacuo
21. 21
    Sonstigethe residue was triturated with ether (30 ml)
22. 22
    workup.WAITto stand at ambient temperature for 72 hours
23. 23
    Filtrationthe resulting solid was collected by filtration
24. 24
    Sonstigedried in vacuo

Vorschrift

A mixture of 3-(benzo[b]thiophen-4-yl)-2-methyl-5,6-dihydroimidazo[2,1-b]thiazole hydrochloride (2 g; prepared in a manner similar to that described in Example 9 Method A), 5M aqueous sodium hydrogencarbonate solution (50 ml) and dichloromethane (50 ml) was stirred at ambient temperature for 30 minutes, then the free base was extracted into dichloromethane (2×50 ml). The combined extracts were dried (MgSO4) and the solvent was removed in vacuo. The residue was dissolved in tetrahydrofuran (40 ml), then the stirred solution was cooled to −70° C. and n-butyllithium (2.5M solution in hexanes; 2.85 ml) was added dropwise under nitrogen. The mixture was stirred at −70° C. for 1 hour, then methyl iodide (0.45 ml) was added dropwise. The mixture was stirred at −70° C. for 1 hour then it was poured into saturated aqueous ammonium chloride solution (50 ml). The product was extracted into ethyl acetate (2×50 ml), the combined extracts were dried (MgSO4) and the solvents were removed in vacuo. The residue was purified via flash chromatography over silica using a 9:1 mixture of dichloromethane and methanol as eluant. Appropriate fractions were combined and the solvents were removed in vacuo. The residue was dissolved in ethanol, concentrated hydrochloric acid (10 drops) was added, the solvent was removed in vacuo, and the residue was triturated with ether (30 ml). The mixture was allowed to stand at ambient temperature for 72 hours then the resulting solid was collected by filtration and dried in vacuo to give 2-methyl-3-(2-methylbenzo[b]thiophen-4-yl)-5,6-dihydroimidazo[2,1-b]thiazole hydrochloride (1.15 g) as a colourless solid, m.p. 271° C.

Quelle