Synthesis of 2-fluoropropenoic acid derivatives

Abstract

A method is described for the synthesis of 2-fluoropropenoic acid esters, amides, and nitrile from the corresponding derivatives of 2-fluoro-3-(4-toluenesulfonyloxy)propanoic acid by heating with potassium phthalimide in vacuo. The free acid Ia and its chloride have also been synthesized. The reactivity of esters and nitrile of acid Ia has been verified by the Michael addition of diethyl acetamidomalonate to these compounds.

Synthesis and Pharmacological Evaluation of Novel γ-Aminobutyric Acid Type B (GABAB) Receptor Agonists as Gastroesophageal Reflux Inhibitors

“…The preparation of the racemic 2-fluoro analogues 7 and 8 was achieved as shown in Scheme . Ethyl (diethoxymethyl)phosphinate ( 14 ) and ethyl (methyl)phosphinate ( 15 ) were both transformed to the corresponding trimethylsilylated P(III) intermediates (structures not shown), which on addition to ethyl 2-fluoroacrylate afforded fluoropropanoates 16 and 17 , respectively. The carboxylic acid ester moiety of 16 and 17 was converted to the corresponding amide, yielding 18 and 19 , respectively, which then were reduced and finally subjected to acidic hydrolyses to afford 7 and 8 , respectively.…”

γ‐Fluorinated Analogues of Glutamic Acid and Glutamine

“…Later on, the same authors optimised both the preparation and the reaction of the Michael acceptor to prepare 4-fluoroglutamic acid 1 on multigram scale. Ethyl 2-fluoroacrylate 5 of high purity was first prepared in quantitative yield by vacuum distillation of a mixture of potassium phthalimide and ethyl 2 -fluoro -3 -(4Ј -toluenesulphonyloxy)propionate (Tolman and Spronglova, 1983;Tolman and Veres, 1964). Freshly prepared ethyl 2-fluoroacrylate 5 was then immediately subjected to Michael addition with diethyl acetamidomalonate 6 to afford the adduct 7 in 80-88% yield.…”

Synthesis of some racemic?-fluoro-?-amino acids

“…The alkylation with a fluorinated carbon fragment of acetamidomalonate can be the key-step. In this way a series of monofluorinated aliphatic amino acids has been prepared (Raasch, 1958;Hudlkck~, 1960Hudlkck~, , 1961Tolman et al, 1967Tolman et al, , 1983Tolman et al, , 1993. Alternatively 2-fluoromalonate and ethyl 2-acetamidoacrylate have been used for the Michael-type bond formation (Buchanan et al, 1962).…”