Ethyl glycinate

For primary amines in the pKa range 10-11, triethylamine (2eq.) suffices as base for less-basic amines, n-BuLi (2eq.) must be used. 

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S g of ethyl glycinate hydrochloride were dissolved in 400 cc of ethanol and 33.5 g of salicylic aldehyde were added. It is refluxed for half an hour and cooled. 38 cc of triethylamlne and 25 g of Raney nickel are then added whereafter hydrogenation is carried out at room temperature and under atmospheric pressure. After hydrogen adsorption was complete, the mixture was filtered and the alcohol evaporated off. The residue was taken up with acidified water, extracted with ether to eliminate part of the by-products, consisting mainly of o-cresol, then made alkaline with ammonia and extracted with ethyl acetate. The solvent was removed in vacuo and the residue crystallized from ether/petroleum ether. 36.7 g of o-hydroxybenzyl-aminoacetlc acid ethyl ester melting at 47°C are obtained. 

Ethyl hexylamine Hexetidine Ethyl glycinate HCI Caroxazone... 

Ethyl glycinate was heated with excess TMSNEt2 in the presence of a catalytic amount of ammonium sulphate at 120 °C, until no more diethylamine distilled out. The product was distilled directly (75%), b.p. 100°C/10mmHg. 

Aldehydes, 43 a-Chiral, 112 a/MJnsaturated, 85,110 /3-Aldchydosi lanes, 22 Aldol reaction, directed, 139 Alkoxytrimethylsilanes, 122 Alkyl lithium. 67 Alkyl silyl ethers, 91-97,127 Alkylation, 33 of ethyl glycinate, 88-89 t-Alkylation, 111-135... 

Enolate generation, 106-7 Enolate trapping, 99-101 Enones, 34-5 Epoxidation, 21-3 a/3-Epoxysilanes, 21-4, 78 -Ethoxy acylsilane, 110 1-Ethoxy-l-trimethylsilyloxycyclo-propane,133 Ethyl bromoacetate, 123 Ethyl 2-chloropropanoate, 133 Ethyl glycinate, 87,88-9 Ethyl m-nitrobenzene, 137 Ethyl irimethylsilylacetate. 71, 123-4, 134 Ethyllithium, 66... 

Ytterbium, trinitratotris(dimethyl sulfoxide)-structure, 1, 97 Ytterbium, tris(acetylacetone)(4-ammo-3-penten-stereochemistry, 1,81 Ytterbium complexes acetylacetone, 2,373 dipositive oxidation state hydrated ions, 3,1109 polypyrazolylborates, 2,255 Ytterbium(III) complexes ethyl glycinate, diacetate... 

The HHT of ethyl glycinate 25 also reacted quantitatively with aliphatic phosphites under comparable conditions to give the corresponding aliphatic glyphosate triester 26, which was identical in all respects to the corresponding Mannich product (31). The product mixture from diethyl thiophosphite was much mote complex and led to dramatically lower yields (27). 

The value of using the preformed HHT with diphenyl phosphite in this procedure was readily apparent from the nearly quantitative conversion to glyphosate observed from 25. A much lower yield (38%) of glyphosate was obtained after hydrolysis when the same components (ethyl glycinate hydrochloride and formaldehyde) were mixed and heated with neat triphenyl phosphite to give triester 30 (43). 

Interestingly, a different ring system was produced when the HHT of ethyl glycinate 25 was employed with ethyl p-chloroethylphosphinate to block cyclization at the carboxyl group. In this case, intramolecular cyclization occurred at nitrogen to give the unusual azaphospholidine oxide 128 in modest isolated yield (74). 

Nssh= (S)-N-(sec-butyl)glycine Nspe= (S)-N-(l-phenylethyl)glycine Ngch = (S)-N-(l-cyclohexyl-ethyl)glycine NLys = N-(4-aminobutyl)glycine. 

The same reagents can be used to form amides from carboxylic acids and amines, a method which is applicable to peptide synthesis. Condensation of A-benzyloxycarbonyl-L-phenylalanine and ethyl glycinate hydrochloride gave an 85% yield of purified dipeptide. 

A different type of synthesis, which leads to a benzannulated indolo[2,3-3][l,6]naphthyridine 15, is illustrated in Scheme 3 <1999TL3797>, and the use of an azaindolone as starting material may introduce an additional heteroatom into the indole moiety of the product, as in 16 (Equation 2) <1994TL1995>. The dipyrrolo[2,3-3 2, 3 -g][l,8]naphthyridine 18 is produced by reaction of the naphthyridine 17 with ethyl glycinate in the presence of a phase-transfer catalyst (Scheme 4) <2000PS(163)29>. 

The behavior of 2-alkylthiohydantoins 428 and 3-chlorobenzopyrano[2,3-c]pyrazole 430 toward er-amino acid derivatives was studied. 2-Alkylthiohydantoins 428 condensed with alanine at high temperature, and the reaction of 3-chlorobenzopyrano[2,3-z]pyrazole 430 with ethyl glycinate was carried out in DMF at reflux to give the cycloadduct 431 in 62% yield (Equations 197 and 198) <2000PS77, 2000FA641>. 

Care must be taken in the choice of organic solvent. Chloroform should never be used under the basic conditions due to the risk of the formation of isocyanides (see Chapter 7) and the use of carbon disulphide can lead to formation of dithiocarba-mates, e.g. dimethyl A -(ethoxycarbonylmethyl)iminodithiocarbonate is formed (35-39%), as the major product in high purity, in the liquiddiquid two-phase methyl-ation of ethyl glycinate in carbon disulphide [15]. The product is useful as an intermediate in the synthesis of thiazoles [15] and dihydrooxazoles [16]. 

Michael addition of methylene imines with alkenes under solid Iiquid two-phase conditions provides a route to substituted a-amino acids [26, 27] (Scheme 6.22). When ethyl glycine is (V-protected with (S)-menthone, C-alkylation under soliddiquid... 

The electron-deficient alkene (5.2 mmol) in MeCN (5 ml) is added to an intimate mixture of powdered K2C03 (1 g) and NaOH (0.2 g), the (S)-menthone-protected ethyl glycine (1.27 g, 5 mmol), and TBA-Br (0.16 g, 0.5 mmol) in MeCN (20 ml). The mixture is stirred for 1 h at 0°C and then filtered. The solid is washed with MeCN (10 ml) and the combined organic solutions are evaporated and the residue is taken up in Et20. The ethereal solution is washed well with H20, dried (MgS04), and evaporated to produce the alkylated imine, which can be converted into the amino acid upon hydrolysis with aqueous acid. 

Stereochemical control of a reaction can also be achieved using non-chiral catalysts, when a chiral centre already exists in the reactant, as for example in the reaction of cyano- or methoxycarbonylmethyl phosphonates with 3-hydroxy-2-(S)-alkylated products are obtained with ca. 40% de of the 2(S)-3(R)-diastereoisomers [11]. Similarly, when ethyl glycine is Ar-protected with (S)-menthone, C-alkylation under soliddiquid conditions using a non-chiral catalyst (6.4.5) provides a route to chiral a-substituted amino acids with optimum enantiomeric excesses of up to 47% [12],... 

Asymmetric induction has been noted [64] when ethyl glycine, protected as its imine by (S)-menthone, is allowed to react with ethyl acrylate under phase-transfer catalytic conditions using tetra-n-butylammonium bromide. An overall yield of 43% was achieved with 46% ee. The stereoselectivity of the reaction was not enhanced when A-benzylquininium or cinchoninium chloride were used and, unlike reactions catalysed by chiral catalysts, the enantiomeric excess increased, when a more polar solvent was used. 

Ma and co-workers extended use of chiral guanidine catalysts to the addition of glycine derivatives to acrylates [121], Addition products were achieved in high yield with modest enantioselectivity (Scheme 67). The ferf-butyl glycinate benzophenone imines generally provided better enantiomeric ratios than the ethyl glycinate benzophenone imines. Based on this observation, the authors hypothesized that an imine-catalyst complex determines the stereochemical outcome of the product. 

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