Hydrochloric Acid → Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

To a solution of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (19.3 g, 84.0 mmol) in THF (100 mL) was added diborane (185 mL, 1.0 M solution in THF) over a period of 10 min at 0° C. Hydrogen gas was rapidly evolved and after gas evolution had ceased the reaction was stirred at room temperature for 1 h. The reaction mixture was again cooled to 0° C., and 1 M aqueous HCl was added dropwise to the reaction mixture with further evolution of hydrogen. Addition of HCl was continued until the evolution of hydrogen had almost ceased. The mixture was then stirred for 10 min and made basic (pH 13-14) by the addition of 1 M NaOH solution. The aqueous solution was extracted with ethyl acetate, the organic phase washed with brine, dried and concentrated under reduced pressure to yield 4-Hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (18.12 g, 100%).

1. temperatureThe reaction mixture was again cooled to 0° C.
2. stirringThe mixture was then stirred for 10 min
3. extractionThe aqueous solution was extracted with ethyl acetate
4. washthe organic phase washed with brine
5. customdried
6. concentrationconcentrated under reduced pressure

ORD record

ord-91d40b688a9b498cabf1e210a690dcf9

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07423012B2