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

Participants

Reaction Steps

1-tert-Butoxycarbonyl-4-piperidone (6.87 g, 0.0345 mol, 1.15 eq) and 4-hydroxypiperidine (3.03 g, 0.03 mol, 1 eq) were stirred at room temperature in ethanol (25 ml) and acetic acid (2 ml) for 2 hours. To the solution was added 0.3 g of 5% palladium on carbon type 5214 Engelhard catalyst. The reaction was then hydrogenated under a pressure of 3.5 bar at room temperature for 24 hours. Further catalyst (0.3 g) was added and the reaction hydrogenated under a pressure of 3.5 bar for a further 19 hours. The catalyst was filtered off through CELITE™, washed with ethanol (10 ml) and evaporated in vacuo to an oil. To the oil was added 20% citric acid (10 ml) and isopropyl acetate (20 ml). The aqueous was collected and basified (10M aqueous sodium hydroxide, 3 ml) and the aqueous washed twice with MTBE (2×25 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 (6.9 g, 79.8% yield; 96.3% purity HPLC area %).

Provenance & Evidence