[81616-20-8]  · C9H16N2O2Si  · 2-(Trimethylsilyl)ethoxycarbonylimidazole  · (MW 212.36)

(introduction of the trimethylsilylethoxycarbonyl protecting group1)

Physical Data: mp 29-30.5 °C;1 bp 99-100 °C/1 mmHg.3

Solubility: insol H2O; sol benzene, ether, THF, chloroform.

Form Supplied in: not commercially available.

Analysis of Reagent Purity: NMR.1

Preparative Method: from 2-(Trimethylsilyl)ethanol and N,N-Carbonyldiimidazole.1

Purification: silica gel chromatography.1

Handling, Storage, and Precautions: stable crystalline solid; possibly moisture sensitive.

Protecting Group Formation.

2-(Trimethylsilyl)ethoxycarbonylimidazole (1) is a useful reagent for the introduction of the 2-trimethylsilylethoxycarbonyl (Teoc) alcohol protecting group. For example, (1) has been used to protect the secondary hydroxyl group of verrucarol (2) as the Teoc derivative (eq 1).1 Note that the apparently low yield (54%) of this reaction is due to the presence of a second reactive hydroxyl group in (2). The yield based on consumed (2) is a more respectable 81%. Although other examples of the use of (1) have not yet been reported, the reagent appears to have significant potential for the protection of alcohols and amines.

Alternative reagents for the introduction of the Teoc group include 2-(Trimethylsilyl)ethyl Chloroformate (3; X = Cl),2 trimethylsilylethyl azidoformate (3; X = N3),2 trimethylsilylethyl methoxyvinyl carbonate (4),3 trimethylsilylethyl 4-nitrophenyl carbonate (5),4 and the aminoxy carbonates (6).7 Of these, only the 4-nitrophenyl carbonate (5) is commercially available. The carbonate (5) has been used to block NH groups in amino acids4,5 and indoles.6

Although (1) is not commercially available, it is a stable, crystalline solid which is readily prepared in excellent yield by condensation of commercially available 2-trimethylsilylethanol and carbonyldiimidazole (eq 2).1 This procedure avoids the use of potentially dangerous phosgene gas which is required for the preparation of the other reagents. Alternatively, (1) may be prepared in a somewhat less convenient manner from (4).3 The stability, easy preparation, and reactivity of (1) combine to make it an excellent reagent for the introduction of the Teoc protecting group.

1. Roush, W. R.; Blizzard, T. A. JOC 1984, 49, 4332.
2. Carpino, L. A.; Tsao, J.-H. CC 1978, 358.
3. Kita, Y.; Haruta, J.; Yasuda, H.; Fukunaga, K.; Shirouchi, Y.; Tamura, Y. JOC 1982, 47, 2697.
4. Wuensch, E.; Moroder, L. Hoppe-Seyler's Z. Physiol. Chem. 1981, 362, 1289 (CA 1982, 96, 7063p).
5. Rosowsky, A.; Wright, J. E. JOC 1983, 48, 1539.
6. Dhanak, D.; Reese, C. B. JCS(P1) 1986, 2181.
7. Shute, R. E.; Rich, D. H. S 1987, 346.

Timothy A. Blizzard

Merck Research Laboratories, Rahway, NJ, USA

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