Hydrochloric Acid → 5-Hydroxymethylimidazo[5,1-b]thiazole

To a solution of 0.929 g of the ethyl imidazo[5,1-b]-thiazole-5-carboxylate obtained in Preparation 9 in 20 ml of methanol was added 0.897 g of sodium borohydride, and the mixture was stirred overnight at room temperature. 2 ml of concentrated hydrochloric acid was added dropwise to the reaction solution with ice-cooling. The mixture was stirred for 10 minutes, and then concentrated to dryness under reduced pressure. The residue was dissolved in 50 ml of methanol, and concentrated to dryness again. To the residue were added 30 ml of an aqueous potassium carbonate solution (50 wt. %) and 30 ml of dichloromethane with ice-cooling. The mixture was stirred for 10 minutes, and then filtered to remove insoluble matters. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (30 ml×2). The combined organic layers were dried over anhydrous potassium carbonate, and purified by flash column chromatography using silica gel, eluting first with ethyl acetate and then with a 20:1 mixture of ethyl acetate and methanol to give 0.628 g (yield 86%) of the title compound as light yellow crystals.

1. temperaturecooling
2. stirringThe mixture was stirred for 10 minutes
3. concentrationconcentrated to dryness under reduced pressure
4. dissolutionThe residue was dissolved in 50 ml of methanol
5. concentrationconcentrated to dryness again
6. additionTo the residue were added 30 ml of an aqueous potassium carbonate solution (50 wt. %) and 30 ml of dichloromethane with ice-
7. temperaturecooling
8. stirringThe mixture was stirred for 10 minutes
9. filtrationfiltered
10. customto remove insoluble matters
11. customThe organic layer was separated
12. extractionthe aqueous layer was extracted with dichloromethane (30 ml×2)
13. dry with materialThe combined organic layers were dried over anhydrous potassium carbonate
14. custompurified by flash column chromatography
15. washeluting first with ethyl acetate
16. additionwith a 20:1 mixture of ethyl acetate and methanol

ORD record

ord-76630dfabb9547df9c654a15b1bf959a

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05663162