Hydrochloric Acid → 2-[4-(1-Methyl-3-piperidin-1-ylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-ene

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Reaction Steps

To a solution of triphenylphosphine (1.03 g, 3.92 mmol, 1.1 eq) in tetrahydrofuran (10 ml) at 0° C. is added dropwise diisopropylazodicarboxylate (0.776 ml, 3.92 mmol, 1.1 eq). The mixture is stirred for 5 minutes and 4-(1-piperidinyl)-2-butanol (0.56 g, 3.56 mmol, 1 eq) is added slowly. Then, a solution of 4-(3-oxa-1-azaspiro[4.5]dec-1-en-2-yl)phenol ax8 (0.82 g, 3.56 mmol, 1 eq) in tetrahydrofuran (5 ml) is added at 0° C. The mixture is allowed to warm at room temperature and stirred for 2 hours. It is then poured into 0.5 N hydrochloric acid and extracted with diethyl ether. The aqueous layer is treated with a 1 M aqueous solution of sodium hydroxide to reach pH 9 and extracted 3 times with diethyl ether. The combined organic layers are dried over magnesium sulfate and the solvent is removed under reduced pressure to give 1.18 g of an orange oil. The crude product is purified by chromatography over silica gel to give 0.41 g of 2-[4-(1-methyl-3-piperidin-1-ylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-ene 37 as a yellow oil.

Provenance & Evidence