Tetrahydrofuran → N-[2-(3-hydroxy-2-pyridyl)propyl]-isopropylamine

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Reaction Steps

To the solution of 10.9 g of 2-methyl-3-hydroxypyridine in 400 ml of tetrahydrofuran, 88 ml of 2.5 molar n-butyllithium in hexane are added dropwise while stirring under nitrogen and keeping the temperature at about 0°. Stirring is continued for 2 hours at 0°-5°, whereupon 0.2 g of isopropyliminoethane are added rapidly and the temperature is maintained at 0°-5°. After stirring the resulting mixture 2 more hours at said temperature, it is poured into 200 ml of saturated aqueous ammonium chloride. The organic layer is separated, evaporated, redissolved in 100 ml of water and the solution extracted 5 times with 50 ml of diethyl ether. The aqueous phase is saturated with sodium chloride, extracted 5 times with 200 ml of methylene chloride, the combined extracts dried, filtered and evaporated. The residue is dissolved in ethanol and the solution neutralized with ethanolic fumaric acid. The resulting suspension is filtered and the residue recrystallized from ethanol, to yield the hemi-fumarate of N-[2-(3-hydroxy-2-pyridyl)propyl]-isopropylamine of Formula II, with R=H, R'=OH and CpH2p±1 =CH(CH3)2, melting at 199°-199.5°.

Provenance & Evidence