The synthesis of r-fluoroglutamic acid, HOOCCIIFCHyCH(.\'I-I2)COOI-I, was achieved by two independent methods, both of which involved the Michael reaction: (1) methyl a-fluoroacrylate and diethyl acetamido~nalonate gave the transesterilied intermediate, which on hydrolysis produced r-lluoroglutamic acid (3lC% yield); (2) ethyl a-acetamidoacrylate and diethyl fluoromalonate reacted under mild conditions to give, after hydrolysis, the required amino acid in 56% overall yield. Of the two procedures, the second is preferable, since it is based on Inore readily available starting ~naterials and gives a higher yield.

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a-Monofluoroalkanoic acids are important intermediates in the synthesis of biologically active fluorine compounds. General methods of preparation have been examined, based on the three following reagents: (a) hydrogen fluoride + N-bromoacetamide; (b) diethyl monofluoromalonate; and (c) perchloryl fluoride. The first of these is the recommended procedure for simple unsubstituted a-fluoro acids; however, the fluoromalonate route is less vigorous, and is therefore the method of choice for those a-fluoro acids that contain labile functional groups.

4-Anzino-2-$zrorobulanoic Acid iMonohydrate (L'Fluoro-GABA") ( I ) ( a ) Dietkyl 2-(p-Nitrobenzai~zido)ethylfElrorovizalonate ( I I )Diethy1 fluoromalonate (3.78 g, 21.2 mmoles) and dry di~l~ethylforrna~llide (40 ml) were added to a solution of sodium ethoxide in ethanol, prepared from sodium (50 mg, 2.17 mg-atoms) and dry ethanol (15 ml). The m i x t~~r e was contained in a 100-m1 three-necked Rask fitted with a stirrer, a reflux condenser with drying tube, and a gas inlet. The flask was purged with dry nitrogen throughout the reaction. After the mixture had been stirred for 15 mill, a solution of N-(9-nitrobenzoyl)ethylet~ei~nille (3.87 g, 20.1 mmoles) (5) in dry dimethylfor~lla1llide (15 ml) was added, and this mixture was stirred a t 40-45'for 60 h. I t was then poured into water, acidified with glacial acetic acid, and extracted twice with ether. The extracts \\.ere washed three times with water and dried over anhydrous MgSOr. Removal of the ether gave pale yellow crystals. B e~~z e n e was added, followed by an excess of petroleum ether (60-8O0), giving 11 (3.49 g, 47%). Two recrystallizations of a small quantity from benzene -petroleum ether (60-80") gave the pure product, m.p. 94-95".Anal. Calcd. for ClGHleFN?Oi: C, 51.89; H , 5.17; N, 7.56. Found: C, 52.07; 13, 4.09; N, 7.33. ( b ) /,-Atilirco-2$uoroblctanoic Acid Monohydrate ( I )Compound I1 (25.0 g, 67.5 mmoles) and concentrated hydrochloric acid (100 ml) were heated under reflux for 75 h. T h e mixture was allowed to cool and water was added. p-Nitrobenzoic acid (10.8 g, 95.5%) was removed by filtration. The filtrate was evaporated to give the syrupy amino acid hydrochloride, which was dissolved in water and stirred with all excess of freshly prepared silver oxide. The mixture was filtered through "S~ipercel", and the filtrate was treated with excess hydrogen sulfide. The mixture was again filtered through "Supercel". The aqueous filtrate was evaporated, whereupon the product (I) crystallized immediately. After being washed with methanol and dried i n aacuo, the crystals had m.p. 201-203". Yield: 5.3 g (657%). Recrystallization from 90% ethanol did not alter the melting point. The infrared spectrum + (Nujol mull) had the follolving bands (cm-I): 1 65O(-NHB def., m), 1 5'32 (ionized carboxyl C=O str., s), + 1 5 6 0 (-Sk13 def., m), and 1054 (C-F str., w).Anal. Calcd. for C,, H10F1\;03: C, 34.53; H, 7.25; N, 10.07. Found: C, 34.27; 11, 7.11; N, 10.36. 4-11 t~zi~~o-2-$zrorohesanoic Acid ( V I ) ( a ) Dielhyl (2-NitrobuLyl)$~~oromalonaLe ( I I I )Diethyl Ruorornalonate (10.68 g, 60 mmoles) was added dropwise with stirring to sodium (46 ing, 1.98 mg-atoms) and dry dioxane (8.8 g) in a 50-1111 three-necked flaslt fitted with a stirrer, a reflux condenser with drying tube, and all addition funnel. After all the sodium had reacted, the resultant mixture was cooled in all ice bath, and hydroquinone (10 mg) was added. 2-Nitro-1-butene (4.0 g, 39.6 mmoles) (6) was then added slowly with vigorous stirring over 25 min. Stirring was continued a t room temperature ...

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