Hydrogenation fluoro removal

Following the biosynthetic mechanism, initial ionization of GDP to the cation followed by the subsequent addition of the IDP unit forms the FDP cation in a reaction that is catalyzed by FPPS prenyltransferase (Scheme 7.1) [2]. The mechanism is based on the findings that the enzyme, which normally catalyzes the addition of GDP to IDP, is also able to catalyze the hydrolysis of GDP [3]. Deuterium experiments of this hydrolysis process either with D O or with (1S)-[1- H] GDP indicated that C—O bond was broken and the chirality of the C-1 carbon of GDP was inverted in this process. In addition, when trifluoromethyl group was present at the C-3 position or fluoro atom at the C-2 position of the allylic substrate, destabilization of the cation has been witnessed as observed on the retard of enzyme reaction [4]. In the elimination step (Scheme 7.1) hydrogen is removed from C-2 of IDP part with simultaneous formation of a double bond. The formation of a trans or cis double bond during the FPPS reaction depends on the spatial orientation of IDP relative to the elongating FDP. In the tranx-prenyltransferases, the GDP... 

Removal of the 2 -sulfonyloxy group of 859 in a basic medium, followed by reaction with metal halides (LiBr and Nal) or hydrogen halides (HCl-1,4-dioxane, HBr-acetone, or0.1% HFin l,4-dioxane-AlF3)gave, byway of the 2,2 -anhydro intermediate 861, the 2 -halo derivatives 862-865. The 2 -deoxy analog 866 and l-(6-deoxy-6-fluoro- ff-D-mannopyranosyl)thy-mine were also prepared from 864 (R = H) and 861 (R = H), respectively. l-(4-Deoxy-4-fluoro-y -D-glucopyranosyl)thymine was obtained by the condensation method. A different kind of nucleoside, 5-(5-deoxy-5-fluoro-2,3-0-isopropylidene-a-D-ribofuranosyl)-l,3-dimethyluracil has also been prepared. ... 

Treatment of intermediate 31 with 2.2 equiv of 4-FB A in EtOH at 72 °C afforded 35 as a white crystalline solid in 90% isolated yield (Scheme 6.9). Hydrogenation in the presence of 5% of Pd/C and 1 equiv of MsOH, efficiently removed the Cbz-protected group. MsOH was used to prevent fluoride reduction resulting in low levels of the des-fluoro by-product. Catalyst filtration, followed by neutralization of the crude reaction mixture with NaOH, afforded free amine 36 as a white crystalline product in 99% isolated yield. Free-amine 36 was isolated as a dihydrate which necessitated drying prior to coupling with oxadiazole chloride 2. 

It was found possible to reduce the ether (XVI) to the primary amine (XVII) by means of hydrogen and Raney nickel, without removing the fluorine atom. This permitted the lengthening of the chain at one end of the molecule, while lengthening at the other end was achieved by cyanoethylation of a higher [Pg.28]

The reduction of 2 - 2 -fluoroethoxyethyl cyanide, using Raney nickel and hydrogen, was examined under a variety of conditions. Defluorination readily took place, but finally conditions were found which permitted the conversion of CN to CHa NH2 without the removal of the fluorine atom, giving 3-2 -fluoro-ethoxypropylamine as a stable distillable liquid. 

Complete exclusion of moisture, short contact time of the reactants, and distillation of the reaction product in vacuo arc required for successful fluorination of (dichloromethyl)ben-zene and its 3- and 4-substituted fluoro and nitro derivatives. The hydrogen fluoride formed in side reactions is immediately removed to prevent polymerization of the (difluorometh-yl)benzenes.14... 

The a-fluoro atom activated by a nitro group in polyfluoro compounds such as 84 and 85 was removed on hydrogenation to the hydroxyimio compounds over a palladium black in methanol.221... 

Dinitrophenyl propyl ether 776 Triethylamine (3 drops) is added to a solution of 1-fluoro-2,4-dinitrobenzene (0.5 g) in propyl alcohol (0.2 g). After 12 h the mixture is acidified with hydrochloric acid, and the oil that separates is extracted in ether (3 X 20 ml). The ethereal extracts are washed with sodium hydrogen carbonate solution, then dried. After removal of the ether, the residue is recrystallized from aqueous methanol. This product (0.4 g) has m.p. 29°. 

A-(2-Hydroxyethyl)-2,4-dinitroaniline 548 Ethanolamine (0.5 g) is shaken at room temperature for 3 h with sodium hydrogen carbonate (1 g), water (10 g), and a solution of 1-fluoro-2,4-dinitrobenzene (0.8 g) in ethanol (20 ml). Then, to remove the excess of fluorodinitro-benzene, glycine (0.2 g) is added, shaking is continued for a further 2 h, the alcohol is removed in a vacuum, and the residue is treated with water. Extraction with ether, evaporation of the ether extract, and recrystallization of the residue from ethanol give reddish-yellow needles (1.62 g, 86.4%), m.p. 92°. 

---