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

Participants

Reaction Steps

1-tert-Butoxycarbonyl-4-piperidone (4 g, 0.0201 mol, 1.3 eq) and 4-hydroxypiperidine (1.56 g, 0.054 mol, 1 eq) were stirred at room temperature in ethanol (20 ml) and acetic acid (2 ml) for 3 hours. To the solution was added 0.56 g of 5% palladium on carbon type 440 Johnson Matthey catalyst. The reaction was then hydrogenated under a pressure of 3 bar at room temperature for 16 hours. The catalyst was filtered off through CELITE™, washed with ethanol (40 ml) and evaporated in vacuo to an oil. The oil was dissolved in water (25 ml) and the aqueous washed twice with dichloromethane (2×20 ml). The aqueous was basified (5M aqueous sodium hydroxide, 12 ml) and the aqueous washed twice with dichloromethane (2×30 ml). The combined organics were 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 (3.13 g, 71.5% yield, 95.4% purity HPLC area %).

Provenance & Evidence