Amino acid esters reaction with, phosgene

Reaction with Phosgene. This reaction of amino acid esters is used for preparing the corresponding isocyanates, especially lysine diisocyanate [4460-02-0] (LDI). LDI is a valuable nonyellowing isocyanate with a functional side group for incorporation in polyurethanes. 

The y-amino-p-hydroxy acid derived oxazolidinones 55 are prepared from the corresponding N-unprotected y-amino-p-hydroxy ester derivatives by reaction with phosgene,1119,391 carbonyl diimidazole,[41] or benzyl chloroformate.[86] Alternatively, cyclization is obtained from the N-carbamate protected derivatives, i.e. from the TV-isopropenyloxycarbonyl derivatives under heating,[381 or from the TV-Boc or N-Z derivatives under basic conditions. [68 81 87] By analogy, the p,y-diamino acid analogue is converted into the imidazolidinone 57 by treatment of the unprotected compound with phosgene.[83 88]... 

N-carboxy anhydrides of amino acids (326), obtained fromN-benzyloxy-amino acids as crystalline derivatives by reaction with phosgene. Acylation of glycine methyl ester by (326) gave the corresponding peptides... 

Phosgene, in the presence of 2,6-dimethylpyridine, reacts with the alkyl esters of 3-amino-2-benzoylcrotonic acid to give 1,3-oxazin-2-ones as the major products [2148]. These products are derived from the reaction of the two molar equivalents of the amino ester with two or three equivalents of phosgene. The reaction of phosgene/2,6-dimethylpyridine with ethyl 3-amino-2-benzoyl-2-pentenoate gave a small yield of 1,3-oxazin-2-one ... 

The linker was prepared starting from serine benzyl ester 68 according to Scheme 30. First, the hydroxyl function was protected as a silyl ether. The amino group was then reacted with phosgene to allow for further reaction with a substituted phenol (the educt). Finally, the benzyl ester was subjected to hydrogenolysis yielding unit 69, with the latter bearing a carboxylic acid function for attachment to the solid support to yield 66 ready for use in combinatorial synthesis. 

The developed solid-phase approach started with the preparation of immobilised ureas 114 obtained via acylation of amino acids linked to acid-labile Sasrin resin 104 with ortho-methoxycarbonyl aryl isocyanates or activated para-nitrophenyl carbamates 113. Alternatively, ureas of type 114 could also be generated by reaction of anthranilic esters 115 with immobilised amino acid-derived isocyanates (easily generated from tethered amino acids with triphosgene or phosgene in toluene in excess of a base such as 2,6-lutidine) or activated carbamates 116 (Scheme 4.1.23). 

Reaction of enamines with phosgene / -Amino-a,/ -ethylenecarboxylic acid esters... 

Typical procedures. AOC- and MPC-amino acids. Method A [379] Amyl chloro-formate Dried phosgene (105 g, 1.06 mol) (for a phosgene source, see Chapter 7) was introduced into a solution of t-amyl alcohol (46 g, 0.52 mol) in dry diethyl ether (500 mL), and then the mixture was cooled to 60 °C in an acetone/dry-ice bath. A solution of pyridine (41 g, 0.52 mol) in dry diethyl ether (500 mL) was added dropwise to the cooled mixture with vigorous stirring. Then the reaction mixture was stored overnight in a deep freezer at —20 °C. The formed pyridine hydrochloride was removed by filtration, and the mother liquor was concentrated to a small volume (about 120 mL) in an ice/water bath under reduced pressure. The product thus obtained was used without further purification in the following reactions. Its purity was determined by acylating a known amount of phenylalanine methyl ester as described below it was found that about 4 mL of the product corresponded to 0.01 mol. The yield was about 60%. 

Benzyl esters of a-amino acids may be formed by reaction of the alcohol with the cyclic anhydride (12) formed between the amino acids and phosgene [37]. 

A V -Carbonyldiimidazole (CDI) is prepared in a convenient and safe procedure from phosgene and imidazole as a non-toxic crystalline compound (m.p. 116-118 °C).[5],[6] It reacts almost quantitatively at room temperature or by short and moderate heating with an equimolar quantity of a carboxylic acid in tetrahydrofuran, chloroform, or similar inert solvents within a few minutes to give the corresponding carboxylic acid imidazolide, which is formed under release of carbon dioxide, together with one equivalent of readily separable and recyclable imidazole.Thus, this reaction leads under very mild conditions to the activation of a carboxylic acid appropriate for transacylation onto a nucleophile with an alcohol to an ester, with an amino compound to an amide or peptide, etc. 

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