2-(piperidin-4-ylamino)ethanol synthesis

Yield:875229-91-7 95%

Reaction Conditions:

Stage #1: tert-butyl 4-[(2-hydroxyethyl)amino]piperidine-1-carboxylatewith trifluoroacetic acid
Stage #2: with hydrogenchloride in methanol at 20; for 0.5 h;
Stage #3: with sodium hydroxide in water at 20; pH=> 10; for 0.25 h;Cooling with ice;

Steps:

8

The 4-(2-ethanolamino)-1-Boc-piperidine (14g, 57.3mmol) was treated with TFA (28mL) ^? for 90mL. The TFA was removed (reduced pressure) and the TFA salt was converted to the HCI salt by treatment with 20% HCl/methanol (140mL, 280mmol HCI) at ambient temperature for 30min. The HCl/methanol was evaporated (reduced pressure) to yield a white solid in quantitative yield. ¹⁹F NMR (MeOD) confirmed complete conversion to the HCI salt.The salt was dissolved in H₂0 (10mL) and cooled in an ice-bath. NaOH (10M, 35mL) was added to pH >10. The solution was warmed to RT and stirred for 15min prior to evaporating to dryness. The residue was triturated with ether/isopropanol(2:1), filtered and evaporated to dryness. The trituration process was repeated until no salt was present in the oil (5x) to yield 7.8g (95%) of a clear oil which solidified on standing.

References:

WO2012/142668,2012,A1 Location in patent:Page/Page column 51