Amino esters from halo acids

The same reagent (/ )-(+) -pantolactone 112 gives good results with a-halo acids that are good precursors for many other compounds such as a-amino acids by nucleophilic displacement. The a-halo acid chlorides 115 are prepared directly from the simple acids 114 and treated with the same tertiary amine EtNMe2 used above to give the unstable ketenes 116 and hence the esters 117 by reaction with (R)-(+) -pantolactone22112. 

Dihydro-l//-l,4-benzodiazepin-2-ones 21 are obtained from o-aminobenzophenones by a cyclocondensation with amino esters under base catalysis or by A -acylation with halo acid chlorides followed by cyclization with ammonia ... 

Examples 1 to 5 in Table 1.1 illustrate simple displacement of a bromide (reactions 1 and 4) or a chloride (reactions 2,3, and 5). Reaction 1 illustrates a radical chain extension reaction that reacts ethylene and methyl bromoacetate 1.17), with AIBN (flzofeis-isobutyronitrile) as a catalyst, to produce the requisite bromo-cster. The reaction is not very selective, however, since it produced a mixture of 1.18 and 1.19. The reaction was not very selective and the observed products arose from addition of one and two equivalents of ethylene, respectively, to 1.17. Subsequent treatment with ammonia, the key reaction for this section, led to a mixture of 4-aminobutanoic acid and 6-aminohexanoic acid, 1.2 and 1.4. In reaction 2, ethyl 4,4,4-trifluoropropanoate (J.20) reacted with PCI3 and bromine to give ethyl 3-bromo-4,4,4-trifluorobutanoate, which reacted with ammonia to give 3-amino-4,4,4-trifluorobutanamide, 1.21. Reaction 3 shows the reaction of P-halo lactic acid (3-chloro-2-hydroxypropanoic acid, 1.22) with 28% aqueous ammonia, in an autoclave, to give isoserine (3-amino-2-hydroxypropanoic acid, 1.23). Both halo-acids l and halo-esters 2 have been converted into hydroxy amino acids typical products are 3-... 

Amino acids may be synthesized by displacement of halide from a-halo acids or esters with ammonia, or Gabriel synthesis. 

Anions derived from Schiff bases of a-amino-acid esters react with various halogenomethanes (CH2BrCI, CH2CIF, CHCIF2) to give the expected a-halo-genomethyl derivatives in (crude) yields of 70—80%. Methods for the preparation of /8-fluoro- and 8, 8-difluoro-a-amino-acids have also been developed. 

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