Formic Acid → Ethyl 1-methylpiperidine-4-carboxylate

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Reaction Steps

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).

Provenance & Evidence