1- ethoxymethyl esters

Chemical Name 2-((2,6-Dichloro-3-methylphenyl)emino] benzoic acid ethoxymethyl ester Common Name Etoclofene Structural Formula ... 

Alkoxyalkyl esters and silyl esters are also easily prepared and cleaved. For example, 2-(trimethylsilyl)ethoxymethyl esters are usually cleaved with HF in acetonitrile by fluoride ion. 

Ester cleavage. The AlClj-PhNMe2 combination is a versatile reagent to cleave methyl, benzyl, methoxymethyl, methylthiomethyl, methoxyethoxymethyl, and /3-(trimethylsilyl)ethoxymethyl esters at room temperature. 

The starting material is prepared by reacting 2-amino-6-methylpyridine with ethoxymethyl-ene-malonic acid diethyl ester and then reacting that product with sodium hydroxide. 

Finally, the carbamoyllithium 122 was prepared by tin-lithium transmetallation at —105 °C from the corresponding carbamoylstannane 121. This tin compound was prepared by addition of tri-n-butyltin lithium to an isocyanate followed by quenching with SEMC1 [2-(trimethylsilyl)ethoxymethyl chloride]. The functionalized intermediate 122 was acylated with the ester 123 to give the product 124 in a model study towards the synthesis of mycalamides (Scheme 33)115. 

Since its introduction in 1986315, the 2-(trimethylsilyl)ethylsuifonyl group has been widely adopted in alkaloid, carbohydrate and amino acid chemistry, it is every bit as stable as the arylsulfonyl groups discussed above it is impervious to the ravages of trifluoroacetic add, hot 6 M HC1, trifluoroborane etherate, or 40% HF in ethanol. Nevertheless, under very specific non-reductive conditions, it can be cleaved. The link with 2-(trimethylsilyl)ethyl esters, 2-(trimethylsilyl)ethoxycarbon-y t derivatives, and 2-(thmethylsilyl)ethoxymethyl ethers hardly needs comment. 

Acetal esters such as methoxymethyl (Mom),P9 (2-methoxyethoxy)methyl (Mem),t l benzyloxymethyl (Bom),P l tetrahydropyranyl,P l 2-(trimethylsilyl)ethoxymethyl (SEM)t l and (methylsulfanyl)methyl (hltm) are sensitive to noild aqueous acids in THE as well as to mild Lewis acids such as magnesium bromide in diethyl ether (2 equiv, rt, l-24h).t l In addition. Bom esters may be cleaved by catalytic hydrogenation.P l In the absence of acid, acetal esters display reactivities typical for unhindered alkyl esters. Surprisingly, these esters... 

As has been demonstrated, 2-(trimethylsilyl)ethoxymethyl (SEM) esters are selectively removed from amino acids and peptide derivatives in the presence of the most common N- and O-protecting groups applied in peptide chemistry including the urethane-type Boc, Z, Fmoc, and Troc as well as Bzl, tBu, and TBDMS ethers.The SEM ester is removed by acidolysis or with a fluoride ion source, e.g. TBAF in THF or HMPA or with aqueous HF in MeCN (—10°C).f l Deprotection with magnesium bromide in EtjO represents an even milder alternative that allows increased selectivity toward fluoride-labile silyl ethers or Fmoc groups. The SEM esters are prepared in 60-80% yield by stirring a mixture of 0.25 M N-protected amino acids in DMF with 0.8 equivalents of SEM-Cl and 1.1 equivalents of lithium carbonate at room temperature for 16 hours. 

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