Hydrochloric Acid → 1-Isopropylpiperidine-4-Carboxylic Acid

Temperature

34 °C

Crude ethyl 1-isopropylpiperidine-4-carboxylate (63.39 g, 318.0 mmol) was dissolved in ethanol (500 mL), and NaOH (25.3 g, 632 mmol) was added. The solution was heated to reflux for 15.75 h at which point it was allowed to cool to 34° C. A solution of ethanolic HCl (220 mL, 2.9 M solution) was added rapidly which caused a mild exotherm and immediate precipitation. The resulting NaCl was filtered using a fritted funnel, and the cloudy filtrate was refiltered through diatomaceous earth. The filtrate was concentrated and dissolved in 50% EtOAc/EtOH (600 mL) and heated on a steam bath. The insoluble material was removed by a filtration through diatomaceous earth, and the resulting filtrate was concentrated to a solid which was dried in a 50° C. vacuum oven to yield 54.09 g of yellow solid (corrected for 0.2 wt % EtOH by 1H-NMR analysis) which is a 99% yield over two steps. No further purification was attempted:

1. temperatureThe solution was heated
2. temperatureto reflux for 15.75 h at which point it
3. customimmediate precipitation
4. filtrationThe resulting NaCl was filtered
5. concentrationThe filtrate was concentrated
6. dissolutiondissolved in 50% EtOAc/EtOH (600 mL)
7. temperatureheated on a steam bath
8. customThe insoluble material was removed by a filtration through diatomaceous earth
9. concentrationthe resulting filtrate was concentrated to a solid which
10. customwas dried in a 50° C. vacuum oven

ORD record

ord-3772be81ade34433844f635f4d5aed9f

Source dataset

uspto-grants-2003_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06635657B1