[766-09-6]  · C7H15N  · 1-Ethylpiperidine  · (MW 113.23)

(hindered nonnucleophilic amine used as base for the generation of tin enolates and aldol-like condensations;1 aryl halide couplings; preparation of anhydrides)

Physical Data: bp 131 °C; fp 18 °C; d 0.824 g cm-3.

Solubility: sol most organic solvents.

Form Supplied in: liquid.

Handling, Storage, and Precautions: the liquid is corrosive and flammable. Bottles of 1-ethylpiperidine should be flushed with nitrogen or argon to prevent exposure to carbon dioxide. The vapors are harmful and care should be taken to avoid absorption through the skin. Use in a fume hood.

Aldol Condensations.

1-Ethylpiperidine is the base of choice for the in situ preparation of divalent tin enolates used in diastereoselective and enantioselective cross-aldol reactions (eq 1).1 Preparation of the tin enolates involves treatment of a ketone with Tin(II) Trifluoromethanesulfonate in the presence of 1-ethylpiperidine. The aldol reaction is selective for the erythro diastereoisomer.2

Enantioselective cross-aldol reactions between ketone-derived tin enolates and aldehydes result from the addition of a chiral nonracemic diamine (eq 2).3 The methodology is useful for cross-aldol reactions between two ketones (eq 3),4 and aldol-like reactions involving acyl-2-oxazolidones,5 acylthiazolidine-2-thiones (eq 4),6 and enantiomerically enriched 4-substituted acylthiazolidine-2-thiones (eq 5).7

Preparation of Anhydrides.

The base is used in preparing symmetrical (eq 6)8 and mixed carboxylic acid anhydrides which are used in amide or peptide synthesis (eq 7).9

Aryl Halide Couplings.

Employment of Copper(I) Iodide and 1-ethylpiperidine as catalysts promotes coupling between aryl halides and alkynes (eq 8).10


Treatment of crotonyl chloride with 1-ethylpiperidine in ethanol yields ethyl vinylacetate, while use of 2,4,6-trimethylpyridine as base produces ethyl trans-crotonate (eq 9).11

1. Mukaiyama, T.; Iwasawa, N.; Stevens, R. W.; Haga, T. T 1984, 40, 1381.
2. (a) Mukaiyama, T.; Stevens, R. W.; Iwasawa, N. CL 1982, 353. (b) Ohshima, M.; Murakami, M.; Mukaiyama, T. CL 1985, 1871.
3. Iwasawa, N.; Mukaiyama, T. CL 1982, 1441.
4. (a) Stevens, R. W.; Iwasawa, N.; Mukaiyama, T. CL 1982, 1459. (b) Mukaiyama, T.; Clark, R. S. J.; Iwasawa, N. CL 1987, 479.
5. Yura, T.; Iwasawa, N.; Mukaiyama, T. CL 1987, 791.
6. Mukaiyama, T.; Iwasawa, N. CL 1982, 1903.
7. (a) Nagao, Y.; Kumagai, T.; Tamai, S.; Abe, T.; Kuramoto, Y.; Taga, T.; Aoyagi, S.; Nagase, Y.; Ochiai, M.; Inoue, Y.; Fujita, E. JACS 1986, 108, 4673. (b) Nagao, Y.; Dai, W.-M.; Ochiai, M.; Tsukagoshi, S.; Fujita, E. JACS 1988, 110, 289.
8. (a) Mestres, R.; Palomo, C. S 1981, 218. (b) Cabre-Castellvi, J.; Palomo-Coll, A.; Palomo-Coll, A. L. S 1981, 616.
9. Zaoral, M. CCC 1962, 27, 1273.
10. Castro, C. E.; Gaughan, E. J.; Owsley, D. C. JOC 1966, 31, 4071.
11. Ozeki, T.; Kusaka, M. BCJ 1967, 40, 1232.

Kirk L. Sorgi

The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA

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