Sodium ethoxide → 5-[2-(2,2,2-Trifluoroethyl)guanidino]-3-hydroxymethyl-1,2,4-thiadiazole

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Reaction Steps

3-(2,2,2-Trifluoroethyl)amino-5-amino-1,2,4-thiadiazole (2.0 g.) and tetrahydropyranyloxyacetamidine hydrochloride (2.0 g.) was added to a solution of sodium ethoxide prepared from sodium (0.46 g.) and alcohol (50 ml.). The resulting mixture was stirred at 20° for 4 hours then heated under reflux for 60 hours. Volatile material was evaporated in vacuo and the residue was shaken with 2 N hydrochloric acid (30 ml.) and ethyl acetate (30 ml.). The aqueous layer was further extracted with ethyl acetate (3×30 ml.) then the pH was adjusted to 10 with 2 N sodium hydroxide. The basified mixture was extracted with ethyl acetate (6×30 ml.) and the combined extracts were dried (MgSO4) and evaporated in vacuo to give the crude product as an oil. It could be purified by fractionation on a silica gel column eluted with ethyl acetate to give 5-[2-(2,2,2-trifluoroethyl)guanidino]-3-hydroxymethyl-1,2,4-thiadiazole, m.p. 123°-125°.

Provenance & Evidence