4071-88-9

Basic information

• Product Name: Ethyl (trimethylsilyl)acetate
• Synonyms: Ethyl (trimethylsilyl)acetate, 98+%;2-(Trimethylsilyl)acetic acid ethyl ester;2-[Dimethyl(methyl)silyl]acetic acid ethyl ester;Ethyl (trimethylsilyl)acetate,97%;(Trimethylsilyl)acetic Acid Ethyl Ester ETSA;Ethyl acetatethree Methylsilicone;Acetic acid, (trimethylsilyl)-, ethyl ester;ETHYL(2-TRIMETHYLSILYL)ACETATE
• CAS NO: 4071-88-9
• Molecular Formula: C₇H₁₆O₂Si
• Molecular Weight: 160.29
• EINECS: 223-783-2
• Product Categories: Si (Classes of Silicon Compounds);Si-(C)4 Compounds;Silicon Compounds (for Synthesis);Synthetic Organic Chemistry
• Mol File: 4071-88-9.mol

Chemical Properties

• Boiling Point: 156-159 °C(lit.)
• Flash Point: 95 °F
• Appearance: clear colorless liquid
• Density: 0.876 g/mL at 25 °C(lit.)
• Vapor Pressure: 2.75mmHg at 25°C
• Refractive Index: n20/D 1.415(lit.)
• Storage Temp.: Flammables area
• Solubility: sol ethereal and chlorinated solvents; reacts with protic solvents.
• Water Solubility: Decomposition
• Sensitive: Moisture Sensitive
• BRN: 1755902
• CAS DataBase Reference: Ethyl (trimethylsilyl)acetate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl (trimethylsilyl)acetate(4071-88-9)
• EPA Substance Registry System: Ethyl (trimethylsilyl)acetate(4071-88-9)

Safety Data

• Statements: 10
• Safety Statements: 16-24/25
• RIDADR: UN 3272 3/PG 3
• WGK Germany: 3
• F: 10-21
• TSCA: Yes
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 4071-88-9(Hazardous Substances Data)

Usage

Uses

1. Used in Organic Synthesis:
Ethyl (trimethylsilyl)acetate is used as a silylating agent and a source of an ethyl acetate anion equivalent in various organic synthesis reactions. Its reactivity with nucleophiles and its tendency to undergo desilylation reactions make it a versatile compound in the field of organic chemistry.
2. Used in the Synthesis of Ethyl-2,2-dibromo-2-(trimethylsilyl)acetate and α,β-Unsaturated Esters:
Ethyl trimethylsilylacetate is utilized in the synthesis of Ethyl-2,2-dibromo-2-(trimethylsilyl)acetate, which is an important intermediate in the production of various pharmaceuticals and agrochemicals. Additionally, it is used in the synthesis of α,β-unsaturated esters, which are key components in the production of flavors, fragrances, and other specialty chemicals.
3. Used in the Silyation of Enolizable Aldehydes and Ketones:
Ethyl trimethylsilylacetate is employed to silylate enolizable aldehydes and ketones, which is a crucial step in many organic synthesis processes. This silyation helps protect the carbonyl group from unwanted reactions, allowing for selective functionalization of other parts of the molecule.
4. Used in Condensation Reactions with Aromatic Aldehydes:
In the presence of a base catalyst, Ethyl trimethylsilylacetate undergoes condensation with aromatic aldehydes to yield β-trimethylsiloxycarboxylates. These compounds are valuable intermediates in the synthesis of various organic compounds, including pharmaceuticals and agrochemicals.
5. Used in the Formation of α,β-Unsaturated Esters with Ketones:
When reacted with ketones, lithium ETSA yields α,β-unsaturated esters, which are important building blocks in the synthesis of various natural products and biologically active compounds.

Preparation

ethyl trimethylsilylacetate synthesis: Available by a Reformatsky reaction from ethyl bromoacetate, and by reaction of trimethylsilylmethylmagnesium chloride with ethyl chloroformate. An alternative approach requires the treatment of ethyl acetate with triphenylmethylsodium followed by chlorotrimethylsilane The use of a nitrogen base with ethyl acetate in THF followed by reaction with chlorotrimethylsilane results in a mixture of C- and O-silylation. The use of HMPA as additive in the reaction medium increases the amount of O-silylation to 90%. Similar methods can be used to prepare analogs.

Purification Methods

Purify it by distilling ca 10g of reagent through a 15cm, Vigreux column (p 11) and then redistilling it through a 21cm glass helices-packed column [Hauze & Hauser J Am Chem Soc 75 994 1953]. Alternatively, dissolve it in Et2O, wash with H2O, dilute Na2CO3, dry over Na2CO3, evaporate Et2O, and distil it through a column of 15 theoretical plates. [Gold et al. J Am Chem Soc 70 2874 1948, Beilstein 4 IV 3974.]

InChI:InChI=1/C7H16O2Si/c1-5-9-7(8)6-10(2,3)4/h5-6H2,1-4H3

Upstream product

• 13170-43-9 (trimethylsilyl)methylmagnesium chloride 
• 541-41-3 chloroformic acid ethyl ester 
• 75-77-4 chloro-trimethyl-silane 
• 141-78-6 ethyl acetate 
• 64-17-5 ethanol 
• 4071-85-6 trimetylsilylketene 
• 37170-41-5 Trimethylsilylessigsaeurevinylester 
• 2344-80-1 Chloromethyltrimethylsilane 
• 105-36-2 ethyl bromoacetate 
• 18295-66-4 1-ethoxy-1-(trimethylsiloxy)ethene 
• 27607-77-8 trimethylsilyl trifluoromethanesulfonate 
• 2345-38-2 trimethylsilylacetic acid 
• 507-20-0 tertiary butyl chloride 
• 1000-62-0 trimethylsilylethoxyacetylene 

Downstream Products

• 1825-62-3 ethyl trimethylsilyl ether 
• 141-78-6 ethyl acetate 
• 107-46-0 Hexamethyldisiloxane 
• 64-19-7 acetic acid 
• 2857-97-8 trimethylsilyl bromide 
• 75-77-4 chloro-trimethyl-silane 
• 352431-93-7 ethyl trans-5-phenyl-3-trimethylsiloxypent-4-enoate 
• 53376-62-8 ethyl 3-hydroxy-5-phenylpentanoate 
• 60623-96-3 β-phenyl-β-trimethylsilyloxybenzenepropanoic acid ethyl ester 
• 14629-60-8 trimethyl(3-phenylpropoxy)silane 
• 35156-36-6 Trimethyl-[(E)-1-methylene-3-(2,6,6-trimethyl-cyclohex-1-enyl)-allyloxy]-silane 
• 15096-08-9 1,1-diphenyl-2-(trimethylsilyl)ethanol 
• 2916-68-9 2-(Trimethylsilyl)ethanol 
• 6651-36-1 1-(Trimethylsilyloxy)cyclohexene 

Relevant articles and documents

Highly syn-selective elimination of peterson anti-adducts to give Z-α,β-unsaturated esters

Peterson adducts have been known to stereospecifically give syn-elimination products upon treatment with base except when the product olefin is in conjugation with an electron-withdrawing group. The missing piece has been put in place by using a catalytic amount of DBU, by which syn-elimination could be effected to provide the thermally less stable Z-olefin from the anti-adduct with high selectivity.

Spiro- and bicycloannulation of sulfoximine-substituted 2-hydroxy-dihydropyrans: Enantioselective synthesis of spiroketals, spiroethers, and oxabicycles and structure of dihydropyran oxocarbenium ions

A modular enantioselective synthesis of spiroketals, spiroethers, and oxabicycles, each containing a dihydropyran subunit, is described. It is based on the 2,2-spiro- and 2,6-bicycloannulation of sulfoximine-substituted 2-hydroxy-dihydropyrans. Key steps of the spiroannulations are the ring-closing metathesis of the corresponding 2,2-oxadienyl and 2,6-dienyl dihydropyrans and Prins cyclization of 2-alkenyl 2-hydroxy-dihydropyrans. Ring-closing metathesis of the corresponding 2,6-dienyl dihydropyrans gave oxabicycles with oxabicyclo[4.3.1]decane skeletons. These routes were extended to the synthesis of spiroketals and spiroethers incorporating additional annulated six-membered rings. Diastereoselective Prins cyclization of mono- and bicyclic 2-alkenyl-2-hydroxy-dihydropyrans was highly selective and afforded chloro-substituted spirocycles. Substituted 2-hydroxy-dihydropyrans were obtained through cyclization of δ-hydroxy ketones, which were synthesized from enantiomerically pure sulfoximine-substituted homoallylic alcohols through lithiation and trapping of the α-lithioalkenylsulfoximines with unsaturated aldehydes, followed by allylic oxidation. Inter- and intramolecular glycosidations of the 2-hydroxy-dihydropyrans with O- and C-nucleophiles proceeded with high stereoselectivities and furnished 2,6-trans-configured glycosides. Dihydropyran oxocarbenium ions are most likely intermediates in the glycosidations. According to ab initio calculations, sulfoximine- and trimethyl-substituted dihydropyran oxocarbenium ions adopt a half-chair-like conformation. The energy difference between the oxocarbenium ion with pseudoaxial and the one with pseudoequatorial methyl groups is very small. A transition state model for their reactions with nucleophiles is proposed. It features a half-chair-like conformation, a pseudoequatorial C6 substituent, and an anti-addition of the nucleophile along an axial trajectory to C2 that produces an anti-periplanar lone pair at the O atom. A similar transition state model allows a general explanation for the trans stereoselectivity of the reactions between C6-substituted dihydropyran oxocarbenium ions and nucleophiles. Spiroannulation of 2-hydroxy-dihydropyrans through RCDEM of the corresponding 2,2-dienyl dihydropyrans and Prins cyclization of 2-alkenyl dihydropyrans gave sulfoximine-substituted unsaturated spiroketals and spiroethers. RCDEM of 2,6-dienyl dihydropyrans afforded oxabicycles. A transition state model for the 2,6-trans-stereoselective glycosidation of dihydropyran oxocarbenium ions is proposed. Copyright

Inter- and intramolecular differentiation of enantiotopic dioxane acetals through oxazaborolidinone-mediated enantioselective ring-cleavage reaction: Kinetic resolution of racemic 1,3-alkanediols and asymmetric desymmetrization of meso-1,3-polyols

Acetals derived from racemic 1,3-alkanediols undergo kinetic resolution in chiral oxazaborolidinonemediated ring-cleavage reaction with nucleophiles such as enol silanes and allylic silanes. Enantioselectivity of the reaction is affected by nucleophiles, the N-sulfonyl groups of oxazaborolidinones, and the substituents attached to the acetal carbon. For disubstituted acetals rac-1 and for trisubstituted acetal rac-2, derived from syn-2,4-dimethyl-1,3-pentanediol, satisfactory enantioselectivity is obtained by using methallylsilane 7b,c as a nucleophile in combination with N-mesyloxazaborolidinone 4a. On the other hand, enantioselective reaction of trisubstituted acetal rac-3b, derived from anti-2,4-dimethyl-1,3-pentanediol, is realized by using silyl ketene acetal 5e in combination with N-tosyloxazaborolidinone 4b. The reaction conditions optimized for the kinetic resolution, or enantiomer differentiating reaction, of the racemic acetals are successfully applied to asymmetric desymmetrization of meso-1,3-polyols through intramolecular differentiation of the enantiotopic acetal moieties of the bis-acetal derivatives. The utility of the ring-cleavage reaction as a method for enantioselective terminal differentiation of prochiral polyols is demonstrated in convergent asymmetric synthesis of pentol derivative 35 corresponding to the C(19)-C(27) ansachain of rifamycin S.

Facile Isomerization of Trimethylsilyl Ketene Acetals to α-Trimethylsilyl Esters Catalyzed by Lanthanoid Trifluoromethanesulfonates

Migration of trimethylsilyl group from oxygen to α-carbon in silyl ketene acetals is effectively catalyzed by lanthanoid triflates under mild conditions.Scope and limitation of this rearrangement are presented.

Preparation and reactivity of persistent and stable silyl-substituted bisketenes

2,3-Bis(trimethylsilyl)-1,3-butadiene-1,4-dione (1) is formed as the only product on thermolysis of 3,4-bis(trimethylsilyl)cyclobut-3-ene-1,2-dione (2), and the rate of ring opening of 2 is comparable to that of substituted cyclobutenes and cyclobutenones. Photolysis of 2 also forms 1, which reacts with ethanol in a stepwise fashion with faster addition of one ethanol molecule to give an isolable monoketene 18, which reacts in a further slower step to give succinate diesters, accompanied by desilylation. 2,3-Bis(tert-butyldimethylsilyl)-1,3-butadiene-1,4-dione (3), prepared analogously to 1, similarly adds one molecule of methanol to give the isolable monoketene 20, which then reacts to give dimethyl 2,3-bis(tert-butyldimethylsilyl)succinate (21) as the major product. The reaction of 1 with H2O is faster than with alcohols and forms (E)- and (Z)-2,3-bis(trimethylsilyl)succinic anhydrides (13) as the first observed products. The reactivity of 1 with different nucleophilic solvents is correlated by the Winstein-Grunwald equation and increases with both solvent ionizing power and solvent nucleophilicity.

Selective formation of alkenes from trimethylsilylmethyl ketones and from acylsilanes

Trimethylsilylmethyl ketones, readily available from acyl chlorides, undergo a Reformatsky-Peterson reaction sequence to give 3-alkenoates regioselectively.Acylsilanes, however, react with either zinc ester enolates or trimethylsilylmethylmagnesium chloride to give the corresponding tertiary alcohols which, depending on their structure, spontaneously undergo either elimination or a Brook rearrangement-Peterson olefination sequence.These reactions allow the selective formation of vinylsilanes.

Palladium Catalyzed Coupling Reaction of α-Bromo Ketones with Hexabutylditin

Palladium-catalyzed reaction of α-bromo ketones with hexabutylditin in the presence of trimethylsilyl chloride gave enol trimethylsilyl ether in moderate to good yields.

A MILD AND FACILE SYNTHESIS OF CARBOXYLIC ANHYDRIDES

Reaction of carboxylic acids with trimethylsilylethoxyacetylene in an inert solvent under mild conditions affords the corresponding carboxylic anhydrides in almost quantitative yields.

Selective γ-Substitution of α,β-Unsaturated Esters via α-Trimethylsilyl β,γ-Unsaturated Esters

In order to achieve selective γ-substitution of α,β-unsaturated esters, we investigated the directive effect of silicon in the reaction of various electrophiles with α-trimethylsilyl β,γ-unsaturated esters.These esters were prepared by nickel-catalyzed vinylation reactions of the lithium enolate of ethyl α-(trimethylsilyl)acetate.The α-silyl β,γ-unsaturated esters reacted with a variety of electrophiles (aldehydes, ketones, acetals, ketals, acid chlorides, and chloro thioethers) in the presence of Lewis acids (titanium tetrachloride and trimethylsilyl trifluoromethanesulfonate) to give exclusively the γ-substituted product in moderate to good yields.In some cases, the primary substitution products underwent additional conversions under the reaction conditions, such as the cyclization of the δ-hydroxyl or δ-keto enoates to dihydropyrones or pyrones, respectively.These α-silyl β,γ-unsaturated esters are effective reagents for achieving complete γ-selective substitution of α,β-unsaturated ester systems.