Morpholine → Ethyl 2-(4-morpholinylmethyl)-1,3-thiazole-4-carboxylate

Participants

Reaction Steps

To a solution of ethyl 2-formyl-1,3-thiazole-4-carboxylate (315 mg) in anhydrous DCM (25 ml) was added morpholine (0.164 ml) and the mixture stirred under nitrogen for 3 h at RT. Sodium triacetoxyborohydride (759 mg) was added and the mixture stirred at RT for 16 h. Sodium bicarbonate (50 ml) and DCM (50 ml) were added and the aqueous layer was extracted with DCM (2×25 ml) using a hydrophobic frit. The solvent was removed in vacuo, the residue was dissolved in DCM (5 ml) and purified by chromatography on silica gel eluting with a gradient of 0-100% ethyl acetate in cyclohexane over 30 min. The solvent was removed in vacuo to give a white solid. The solid was dissolved in methanol (15 ml) and loaded onto an SCX SPE cartridge (50 g), which was preconditioned with methanol and allowed to stand for 15 min. The column was washed with methanol (50 ml) and elution with 2M ammonia in ethanol gave the title compound.

Provenance & Evidence