3-Hydroxypyridine → (S)-1-Methyl-5-((pyridin-3-yloxy)methyl)pyrrolidin-2-one

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Reaction Steps

To a stirred solution of 1.57 g (6.0 mmole) triphenylphosphine in 30 ml dry tetrahydrofuran under argon atmosphere at −15° C. 0.95 ml (1.05 g, 6.0 mmole) diethyl azodicarboxylate was added, drop by drop for 5 minutes, then 0.517 g (4.0 mmole) (S)-5-(hydroxymethyl)-1-methylpyrrolidin-2-one in 5 ml dry tetrahydrofuran and 0.40 g (4.2 mmole) 3-hydroxypyridine were added and stirred for 10 minutes, then kept overnight in a refrigerator at −20° C. The solution was evaporated at 35° C. in good vacuum; the residue was dissolved in 15 ml of dichloromethane and washed with 1×7 and 2×2 ml of 1M hydrochloric acid. To the combined acidic solutions 20 ml saturated aqueous sodium bicarbonate solution was carefully added and then further 1 g of solid sodium bicarbonate was added, and this was extracted with 5×10 ml dichloromethane. The combined organic solutions were dried over magnesium sulfate, evaporated on a rotavapor at 35° C. and the residue was purified by column chromatography on 30 g silica gel, and developing with benzene containing 30% of diethylamine; this furnished 0.252 g (31%) of pure product.

Provenance & Evidence