1-Cyclopropylpiperidin-4-one

Uses

1-Cyclopropylpiperidin-4-one

Synthesis

Step 2: A solution of ethyl 3-[cyclopropyl-(2-ethoxycarbonyl-ethyl)-amino]-propionate (39 mmol) in anhydrous tetrahydrofuran (65 mL) was added slowly and dropwise to a solution of sodium hydride (60% oil dispersion, 58 mmol) in anhydrous tetrahydrofuran (65 mL). Anhydrous ethanol (39 mmol) was then added. The reaction mixture was heated under reflux conditions for 24 hours. Upon completion of the reaction, the reaction solution was neutralized with dilute acetic acid to pH 7 and subsequently partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate, the organic phases were combined and dried over sodium sulfate. The solvent was removed by concentration under reduced pressure to give 10.2 g of red oily material. This crude product was mixed with 18% w/w hydrochloric acid (130 mL) and heated at reflux for 5 hours. At the end of the reaction, the pH was adjusted to about 12 with sodium hydroxide (about 31 g) and the crude mixture was extracted with ethyl acetate. The organic phases were combined and dried with sodium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by fractional distillation under reduced pressure (20 mbar) and the fractions with a boiling point of 75 °C (20 mbar) were collected to give 3.6 g (67% yield) of the target product 1-cyclopropyl-piperidin-4-one as a colorless oil. Mass spectrometry (MS) analysis showed m/e: 140.0 (MH+, 100%).

References

[1] Patent: US2006/160855, 2006, A1. Location in patent: Page/Page column 14
[2] Patent: WO2005/123716, 2005, A1. Location in patent: Page/Page column 101
[3] Chemical and Pharmaceutical Bulletin, 1980, vol. 28, # 9, p. 2653 - 2657