Acetic Acid → tert-Butyl 4-hydroxy-[1,4'-bipiperidine]-1'-carboxylate

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Reaction Steps

1-tert-Butoxycarbonyl-4-piperidone (4.02 g, 0.0217 mol, 1.3 eq) and 4-hydroxypiperidine (1.57 g, 0.0155 mol, 1 eq) were stirred at room temperature in ethanol (18 ml) and acetic acid (2 ml) for 10 minutes. To the solution was added 0.62 g of 5% palladium on carbon type 437 Johnson Matthey catalyst. The reaction was then hydrogenated under a pressure of between 4 and 4.5 bar at room temperature for 26 hours. The catalyst was filtered off through CELITE™, washed with ethanol (40 ml) and evaporated in vacuo to an oil. To the oil was added acetic acid (1 ml) and the oil partitioned between water (20 ml) and dichloromethane (30 ml). The aqueous was collected and basified (5M aqueous sodium hydroxide, 5 ml) and the aqueous washed twice with dichloromethane (2×20 ml). The combined organics were washed with brine and dried (magnesium sulphate). The solution was filtered and evaporated in vacuo to give 4-(hydroxy)-[1,4′]bipiperidinyl-1′-carboxylic acid tert-butyl ester as a yellow oil (2.03 g, 46% yield; 92.1% purity HPLC area %).

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