[13475-12-6]  · C5H13NOSi  · N-Trimethylsilylacetamide  · (MW 131.28)

(silylating agent of alcohols2 and carboxylic acids;4 acetamide dianion equivalent;7 aminating agent)

Alternate Name: MSA.

Physical Data: mp 46-49 °C; bp 84 °C/18 mmHg; fp 57 °C.

Form Supplied in: moist white crystals.

Handling, Storage, and Precautions: handle and store under nitrogen; combustible and easily hydrolyzed.

Silylating Reagent.

N-Trimethylsilylacetamide has poor silylation potential1 and although not as frequently used as N,O-Bis(trimethylsilyl)acetamide (BSA) as a silylating agent, this reagent has found a number of uses. N-Trimethylsilylacetamide has been used to silylate alcohols,2 the hydroxy groups of sugars,3 carboxylic acids,4 amino groups,5 and the oxygen of phosphate esters (eqs 1 and 2).6

Acetamide Dianion Equivalent.

The dianion of N-trimethylsilylacetamide can be used as a soluble alternate to the insoluble acetamide dianion. The dianion can be alkylated or acylated at carbon (eqs 3-5).7

In an unusual reaction, N-trimethylsilylacetamide in the presence of Trifluoromethanesulfonic Anhydride can be used to N-glycosylate the anomeric positions of sugars (eq 6).8

Related Reagents.


1. For reviews on silylations, see: (a) Klebe, J. F. ACR 1970, 3, 299. (b) Cooper, B. E. CI(L) 1978, 794.
2. Oppolzer, W.; Snowden, R. L.; Simmons, D. P. HCA 1981, 64, 2002.
3. Birkofer, L.; Ritter, A.; Bentz, F. CB 1964, 97, 2196.
4. Wheeler, W. J.; Finley, D. R.; Osborne, H. E. J. Antibiotics 1980, 33, 72.
5. Atkins, R. K. TL 1986, 27, 2451.
6. Bertrand, R. D.; Berwin, H. J.; McEwen, G. K.; Verkade, J. G. Phosphorus 1974, 4, 81.
7. Kuzma, P. C.; Brown, L. E.; Harris, T. M. JOC 1984, 49, 2015.
8. Kahne, D.; Walker, S.; Cheng Y.; Van Engen, D. JACS 1989, 111, 6881.

Janet Wisniewski Grissom

University of Utah, Salt Lake City, UT, USA

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