Sodium Hydroxide → 2-[(4-Benzyloxy-1-piperidinyl)methyl]-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine

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Reaction Conditions

Reaction Steps

In ethyl acetate was suspended 2.0 g of 4-benzyloxypiperidine hydrochloride and the suspension was neutralized with aqueous 1N-auqeous sodium hydroxide. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The pooled organic layer was washed with water and saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. To a solution prepared by dissolving the resulting 4-benzyloxypiperidine in 0.5 mL of toluene were added 1.1 g of 2-bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine and 2.8 mL of triethylamine, and in an autoclave, the mixture was stirred under nitrogen gas at 180° C. for 15 hours. This reaction mixture was diluted with saturated aqueous NaHCO3 and extracted with 3 portions of ethyl acetate. The pooled organic layer was washed with water and saturated aqueous NaCl, dried over MgSO4, and filtered and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane/ethyl acetate=1:1) and recrystallized from ethyl acetate/hexane to provide 1.1 g of the title compound. Yield 67%.

Provenance & Evidence