Sodium hydride → 6-(2-Methoxybenzyl)-8-phenyl-1,6-diazabicyclo[3.2.1]octane

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Reaction Steps

Sodium hydride (1.47 g, 36.8 mmol of a 60% dispersion in oil) was added to a round-bottomed flask fitted with an N2 inlet, condenser, stirrer and washed with hexane to remove the oil. Anhydrous tetrahydrofuran (THF), 50 mL, was added followed by 6.30 grams (18.9 mmol) of (2S, 3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine in 50 mL of tetrahydrofuran. After heating to reflux for two hours, the mixture was allowed to cool to room temperature and was treated dropwise with benzyl chloromethyl ether (5.1 mL, 36.8 mmol). The mixture was stirred overnight and the excess sodium hydride quenched with water. After being stirred an additional hour, the organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layers were combined and washed with saturated aqueous sodium chloride before drying over magnesium sulfate. Concentration in vacuo gave a solid which recrystallized from methanol/methylene chloride to a white solid, 2.36 grams (40%), mp 105-107° C. Mass Spectrum (m/e): 309 (M+1, 100%), 159 (12%). 1H-NMR (CDCl3)δ 1.45-2.20 (m, 5H), 3.15 (m, 2H), 3.5 (d, 1H), 3.65-3.85 (m, 2H), 3.75 (s, 3H), 3.95 d,1H), 4.10 (d, 1H), 6.8 (d, 1H), 6.95 (t, 1H), 7.15-7.6 (m, 7H). Anal. Calc'd for C20H24N2O; C, 77.88; H, 7.83, N, 9.08. Found: C, 77.72; H, 7.75; N, 9.04.

Provenance & Evidence