Aminoacetic acid esters

Alkylation of trifluoro- and trichloroacetamides with a-bromoacetic esters has been utilized for the synthesis of a wide range of a-aminoacetic acids [11-13] (Table 5.13). Hydrolysis of the intermediate a-trihaloacetamidoacetic esters with methanolic potassium hydroxide converts the methyl and ethyl esters directly into the amino carboxylic acids. /-Butyl a-aminoacetates are more stable, but they are hydrolysed under phase-transfer catalytic conditions (see Chapter 9.2). Reaction of the trihaloacetamides with 1,4-dibromobutane and 1,5-dibromopentane and subsequent hydrolysis provides a simple route to pyrrolidine-2-carboxylic acid (75%) and piperidine-2-carboxylic acid (58%) [11, 12],... 

An unusual BMMA reagent, A -[bis(methylthio)methylene]aminoacetic acid ethyl ester, leads to the annulation of 446b, thereby forming compound 448 (Scheme 35) <1995H(40)851>. 

Fig. 10. (W,)2 parameter used in Eq. 51. The figure depicts the OR2 moiety of the cyclohexyl esters of L-asparthyl-aminoacetic acid (31)611 (reproduced with permission from the American Chemical Society)...

The Gabriel-malonic ester synthesis begins with (V-phthalimidomalonic ester. Think of (V-phthalimidomalonic ester as a molecule of glycine (aminoacetic acid) with the amino group protected as an amide (a phthalimide in this case) to keep it from acting as a nucleophile. The acid is protected as an ethyl ester, and the a position is further activated by the additional (temporary) ester group of diethyl malonate. 

Diazoacetic Acid, Methyl Ester or Methyldiozo acetate (called Diazoessigsaure-methylester in Ger), N2CH.CO2.CH3 mw 100.08, N 27.99% It-yel expl liq, bp 31° at 12mm Hg discillacion, even under reduced pressure, is extremely dangerous, since heat causes the cotnpd to detonate violently d 1,158 at 25° Hq 1.4515 11 31,4676 at 20.6° was prepd by diazotization of aminoacetic acid methyl ester with HNO2 (Refs 1, 2 8 3) ... 

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 triethylamine 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 pert 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-aminoacetic acid ethyl ester melting at 47 C are obtained. 

Just as the malonic ester synthesis gives substituted acetic acids, the A/-phthalimidoma-lonic ester synthesis gives substituted aminoacetic acids a-amino acids. A-Phthalimido-malonic ester is alkylated in the same way as malonic ester. When the alkylated A-phthalimidomalonic ester is hydrolyzed, the phthalimido group is hydrolyzed along with the ester groups. The product is an alkylated aminomalonic add Decarboxylation gives a racemic a-amino add. 

Cellulose chloroacetates (30) and aminoacetates (30,31), acetate sorbates (32), and acetate maleates (33) have been prepared but are not commercially important. These esters are made from hydrolyzed cellulose acetate with the appropriate anhydride or acid chloride in pyridine. 

Heating the aminoacetal (2.1) with ethanolic hydrogen chloride produces a quinoline [2612], but sulphuric acid causes the cyclization to follow another course (see Chapter 3, Section II. 1). n-Aminoaldehydes are cyclized by heating with a reactive methylene-containing ketone, ester or nitrile but in the reaction with the pyrazole aldehyde (2.2), yields seem to depend greatly on the nature of the A -substituent for example, when R = R = CN, the product is obtained in either 3.6% or 83% yields according to whether R is methyl or phenyl [2798]. The chemistry of a-cyanothioacetamide (2.4), which is used in the conversion of 2-aminobenzaldehyde (2.3) to 2-aminoquinoline-3-thiocarboxamide [2926], has been reviewed [3331]. 

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