2-Aminothiazole → 4-(Phenylmethyl)-N-2-thiazolyl-1-piperidinepropanamine

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Reaction Steps

To a solution of 4-benzylpiperidine (3.51 g, 20.0 mmol) and DBU (0.030 ml, 0.20 mmol) in THF (40 ml) was dropwise added a solution of acrolein (90%, 1.485 ml, 20.0 mmol) in THF (10 ml) at −20° C. with stirring over a period of 10 minutes. The mixture was stirred for 1 hour while the temperature of the mixture is elevated from −20° C. to −10° C. To the mixture were added 2-amino-1,3-thiazole (2.00 g, 20.0 mmol) and sodium triacetoxyborohydride (8.48 g, 40.0 mmol), successively, at −10° C., and the mixture was stirred for 15 hours while the temperature of the mixture is elevated to room temperature. Under ice cooling, aqueous solution of 1N-sodium hydroxide (120 ml) was added, and the mixture was stirred for 30 minutes and extracted with diethyl ether (60 ml×4). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The concentrate was subjected to column chromatography (silica gel 100 g, ethyl acetate/methanol=1/0 to 85/15), and the desired fraction was concentrated under reduced pressure to give the titled compound (680 mg, 2.16 mmol) as white crystals. Yield 11%.

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