Pyridine → 8-Hydroxy-8-(6-methoxy-3-pyridyl)-1,4-dioxaspiro[4.5]decane

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Reaction Conditions

Reaction Steps

In a dried 3-neck flask, 5-bromo-2-methoxypyridine (12.6 g, 67.2 mmol) was dissolved in dry THF (130 mL) and cooled to −78° C. under N2. 2.5M n-BuLi in hexanes (28.2 mL, 70.4 mmol) was added dropwise and the mixture stirred at −78° C. for 50 min. To pyridine mixture was slowly added a solution of 1,4-cyclohexanedione mono-ethylene ketal (10.0 g, 64.0 mmol) in dry THF (25 mL). The resulting mixture was stirred at −78° C. for 80 min. The reaction was quenched with sat'd NH4Cl and extracted with CH2Cl2 (3×). The combined extracts were dried (MgSO4), filtered, and concentrated to give a yellow oil. Flash chromatography on silica gel eluting with 10% MeOH/CH2Cl2 afforded the title compound as a yellow solid; yield 16.5 g, 62.2 mmol, 97%; 1H NMR (CDCl3) δ 8.26 (s, 1H), 7.72 (d, 1H), 6.69 (d, 1H), 3.96 (t, 4H), 3.91 (s, 3H), 2.21 (s, 1H), 2.08 (m, 4H), 1.82 (m, 2H), 1.66 (m, 2H); MS m/z=266.1 (M+H)+.

Provenance & Evidence