2-(Trimethylsilyl)ethyl Chloroformate

[20160-60-5]  · C6H13ClO2Si  · 2-(Trimethylsilyl)ethyl Chloroformate  · (MW 180.73)

(introduction of the trimethylsilylethoxycarbonyl (Teoc) protecting group for amines1-3 or alcohols;4,5 activation of tertiary amines for dealkylation6 or ring opening;7-10 starting material for alternative reagents for introduction of the trimethylsilylethoxycarbonyl protecting group11)

Physical Data: bp 34 °C/1 mmHg;6 bp 42-43 °C/4 mmHg;12 d 0.9944 g cm-3.1

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

Form Supplied in: not commercially available.

Analysis of Reagent Purity: NMR.

Preparative Method: prepared from 2-(Trimethylsilyl)ethanol and Phosgene.6,11,12

Purification: distillation.

Handling, Storage, and Precautions: moisture sensitive; stable for three months under nitrogen at 0 °C;6 probably toxic; handle in a fume hood.

Protection of Amines.1

2-(Trimethylsilyl)ethyl chloroformate (1) is a useful reagent for the introduction of the trimethylsilylethoxycarbonyl (Teoc) protecting group for amines.1-3 For example, p-chloroaniline reacts with (1) to form the expected trimethylsilylethyl carbamate (eq 1).1 The Teoc protecting group is stable to hydrogenation (H2, Palladium on Carbon) and mild acid or base. It can be removed with fluoride ion or with a strong acid (e.g. Trifluoroacetic Acid). It is possible to selectively cleave a t-butyldimethylsilyl (TBDMS) ether in the presence of a trimethylsilylethyl carbamate (eq 2).3 For a discussion of alternative reagents for the introduction of the Teoc group, see 2-(Trimethylsilyl)ethoxycarbonylimidazole.

Protection of Alcohols.4

2-(Trimethylsilyl)ethyl chloroformate (1) is also useful for the introduction of the trimethylsilylethoxycarbonyl (Teoc) protecting group for alcohols.4,5 The Teoc protecting group is stable to mild acid but it is base sensitive. It can be cleaved with fluoride ion or with Zinc Chloride or Zinc Bromide (eq 3).4

Dealkylation or Ring Opening of Tertiary Amines.6-10

Under certain conditions, 2-(trimethylsilyl)ethyl chloroformate (1) is reactive enough to acylate a tertiary amine. The resulting quaternary ammonium species is a sufficiently good leaving group for one of the carbon-nitrogen bonds to be cleaved by reaction with a suitable nucleophile. This process has been used to debenzylate tertiary amines (eq 4).6 Subsequent removal of the Teoc group (see above) to afford the free amine results in a net debenzylation of the tertiary amine. Demethylation of tertiary amines is also possible but yields are generally lower.6 Alternatively, for cyclic tertiary amines, acylation of the nitrogen followed by reaction with a nucleophile can result in a ring-opening reaction (eq 5).7 In a strained ring system (e.g. an aziridine), acylation of the nitrogen followed by reaction with a nucleophile can result in ring opening even for secondary amines (eq 6).8

Synthesis of Alternative Teoc Reagents.11

The chloroformate (1) has been used as a starting material for the preparation of alternative reagents for the introduction of the Teoc group (eq 7).11 For a discussion of additional alternative reagents for the introduction of the Teoc group, see 2-(Trimethylsilyl)ethoxycarbonylimidazole.


1. Carpino, L. A.; Tsao, J.-H. CC 1978, 358.
2. Trost, B. M.; Cossy, J. JACS 1982, 104, 6881.
3. Trost, B. M.; Romero, A. G. JOC 1986, 51, 2332.
4. Gioeli, C.; Balgobin, N.; Josephson, S.; Chattopadhyaya, J. B. TL 1981, 22, 969.
5. Schuda, P. F.; Ammon, H. L.; Heimann, M. R.; Bhattacharjee, S. JOC 1982, 47, 3434.
6. Campbell, A. L.; Pilipauskas, D. R.; Khanna, I. K.; Rhodes, R. A. TL 1987, 28, 2331.
7. Toth, J. E.; Fuchs, P. L. JOC 1986, 51, 2594.
8. Legters, J.; Willems, J. G. H.; Thijs, L.; Zwanenburg, B. RTC 1992, 111, 59.
9. Kim, G.; Chu-Moyer, M. Y.; Danishefsky, S. J. JACS 1990, 112, 2003.
10. Kim, G.; Chu-Moyer, M. Y.; Danishefsky, S. J.; Schulte, G. K. JACS 1993, 115, 30.
11. Shute, R. E.; Rich, D. H. S 1987, 346.
12. Kozyukov, V. P.; Sheludyakov, V. D.; Mironov, V. F. JGU 1968, 38, 1133.

Timothy A. Blizzard

Merck Research Laboratories, Rahway, NJ, USA



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