2-Methyl-5-hydroxypyridine → 2-Methyl-5-(1-(phenylthio)cyclopropoxy)pyridine

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Reaction Steps

Cyclopropylphenylthioether (5.0 g, 33.3 mmol) was dissolved in tetrahydrofuran (50 mL), and n-butyllithium (25.1 mL, 39.9 mmol) was dropped for 5 minutes under an argon atmosphere at 0° C. Then, at −78° C., a solution of N-iodosuccinimide (8.99 g, 39.9 mmol) in tetrahydrofuran (100 mL) was dropped. The mixture was stirred overnight and allowed to warm gradually to room temperature. The reaction solution was added a saturated aqueous solution of sodium hydrogen carbonate, and extracted with hexane. The organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by silica-gel column chromatography (hexane). A crude product (5.64 g) ((1-iodocyclopropyl)(phenyl)sulfane:cyclopropylphenylthioether=2.4:1) was obtained. Then, 5-hydroxy-2-methylpyridine (1.82 g, 16.7 mmol) was dissolved in toluene (150 mL), added silver carbonate (9.19 g, 33.3 mmol), and a mixture of (1-iodocyclopropyl)(phenyl)sulfane:cyclopropylphenylthioether (=2.4:1) (5.64 g, 16.7 mmol (*converted in terms of the amount of (1-iodocyclopropyl)(phenyl) sulfane), and the mixture was stirred at room temperature overnight. Then, acetic acid (200 mL) was added and stirred for 10 minutes. The reaction solution was filtered through a pad of celite, and concentrated in vacuo. The obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate), and the title compound (1.88 g (yield 44%)) was obtained as a yellow oil.

Provenance & Evidence