Diethyl 2-fluoromalonate

Compound (VIII.98), a folic acid analogue with a y-fluoro substituent in the side-chain was described first by Alekseeva e/ al. [281] and several years later by Bergmann and Chun-Hsu [282]. The synthesis of (VIII.98), as mixture of threo and erythro isomers, was achieved via the Waller method from V-(4-ami-nobenzoyl)-y-fluoroglutamic acid, 2,4,5-triamino-6(lif)-pyrimidinone, and 2,3-dibromopropionaldehyde, but the yield was low (5.6%). y-Fluoroglutamic acid, as a mixture of D- and L-enantiomers, was prepared from diethyl 2-fluoromalonate by condensation with ethyl 2-acetamidoacrylate followed by hydrolysis and decarboxylation in refluxing 12 M HCl, or from ethyl 3-chloro-2-hydroxypropanoate by a sequence consisting of (i) 0-t-butylation with CH2 = C(CH3)2, (ii) condensation with diethyl 2-acetamidomalonate, (hi)... 

Several electrophilic groups can be opened by malonate anions. In one interesting example, aziridine derivatives were opened, as in the condensation of 4.57 with diethyl 2-fluoromalonate to give 4.58. Subsequent treatment with aqueous HCl gave 4-amino-2-fluorobutanoic acid, 4.59.21 Another strategy using a different... 

Diethyl malonatc13 gives four products upon reaction with perchloryl fluoride diethyl difluoro-malonate, diethyl ethylmalonate, diethyl ethylfluoromalonate and diethyl fluoromalonate the product distribution depends on the reaction conditions. A number of esters are fluo-rinated,14 15 while (pentafluorophenyl)acetonitrile is converted into mono- and disubstituted products in the presence of cesium fluoride.16... 

Diesters are malonates. Barbiturates are often made from substituted malonates by this route. Thus the reaction between diethyl fluoromalonate and (V-methylurea gave 5-fluoro-l-methyl-2,4,6(l//,3//,5//)-pyrimidinetrione (569) <84CL1573>. 

Fluoromalonates can be obtained in moderate yields by fluorination of the corresponding carbanions with xenon difluoride, dimethyl sulfide and boron trifluoride-diethyl ether complex.29... 

Substituted diethyl l-(ethoxycarbonyl)-l-fluoromethylphosphonates bearing acyL " "" or alkoxycarbonyk groups in a-position, on room temperature treatment with MgCl2/NH4Ck"" or wet silica gel/AcOEt,"" produce the corresponding a-fluoro-P-keto esters and fluoromalonates in very good yields (83-92%, Scheme 3.61). - ... 

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