Formic Acid → Ethyl 1-methylpiperidine-4-carboxylate

To ethyl isonipecotate (10 g, 64 mmol) was slowly added a 37% aqueous solution of formaldehyde (10 mL, 128 mmol) followed by formic acid (10 mL, 233 mmol) and the mixture was heated to reflux for about 3 days. The mixture was allowed to cool to room temperature, the pH was adjusted to 2 by addition of concentrated hydrochloric acid and the mixture was extracted with ethyl acetate. The pH of the aqueous layer was then adjusted to 11 by addition of 2N aqueous sodium hydroxide, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts of the second extraction were dried (MgSO4), filtered, and concentrated under vacuum to provide the desired product. 1H NMR (500 MHz, CDCl3-d): δ 1.25 (t, J=6 Hz, 3H), 1.40 (m, 1H), 1.59 (m, 1H), 1.62 (m, 1H), 1.95 (m, 2H), 2.06 (m, 1H), 2.26 (s, 3H), 2.71 (m, 1H), 2.94 (m, 1H), 4.13 (dd, J=6 Hz, 2H).

1. temperaturethe mixture was heated
2. temperatureto reflux for about 3 days
3. extractionthe mixture was extracted with ethyl acetate
4. additionThe pH of the aqueous layer was then adjusted to 11 by addition of 2N aqueous sodium hydroxide
5. extractionthe aqueous layer was extracted with ethyl acetate
6. extractionThe combined organic extracts of the second extraction
7. dry with materialwere dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated under vacuum

ORD record

ord-f41873040ba34a939bb4fd6ecadc1703

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468371B2