These common heterocyclic compound, 327-52-6, name is 1-Bromo-2,4,5-trifluorobenzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Product Details of 327-52-6
This example illustrates step 2 of the process of the invention: Heck coupling of 1-bromo-2,4,5-trifluorobenzene with 1-benzyl-4-methyl-2-methylenesuccinate with selective formation of (E)-1-benzyl-4-methyl-2-(2,4,5-trifluorobenzylidene)succinate, compound (IV). [Show Image] A 1000 mL round bottomed flask fitted with magnetic stirrer, thermometer, nitrogen inlet and reflux condenser is charged with 1-benzyl-4-methyl-2-methylenesuccinate (100.0 g, 0.43 mol), 1-bromo-2,4,5-trifluorobenzene (124.0 g, 0.59 mol), methyl dicyclohexyl amine (127.0 g, 0.65 mol), dimethyl acetamide (215 mL), water (53 mL) and lithium bromide (7.5 g, 0.09 mol). The mixture is degassed with three vacuum-nitrogen cycles; palladium acetate (260 mg, 1.16 10-3 mol) is then added as reaction catalyst. The mixture is heated with stirring at 95-98 C for 22 hours monitoring by GC until > 95% conversion, then cooled to room temperature, added of water (500 mL) and toluene (250 mL) and filtered on a Celite pad. The organic phase is washed with 1N HCl (200 mL), dried by azeotropic distillation under reduced pressure, treated with coarse silica gel (20 g), filtered and concentrated to a residue (128 g). Gas-chromatographic analysis of the crude product shows the following composition: 87% (E)-1-benzyl-4-methyl-2-(2,4,5-trifluorobenzylidene)succinate, 7% (Z)-1-benzyl-4-methyl-2-(2,4,5-trifluorobenzylidene)succinate, 4% (E)- and (Z)-1-benzyl-4-methyl 2-(2,4,5-trifluorobenzyl)maleate, 2% starting material. An analytical sample of pure (E)-1-benzyl-4-methyl-2-(2,4,5-trifluorobenzylidene)succinate is obtained by flash chromatography with gradient elution 0?20% AcOEt in hexane. 1H NMR (300 MHz, CDCl3) delta 7.77 (s, 1H), 7.40-7.34 (m, 5H), 7.22 (ddd, J=15.3, 8.6, 6.7 Hz, 1 H), 6.97 (ddd, J=15.9, 15.9, 6.4 Hz, 1 H), 5.26 (s, 2H), 3.66 (s, 3H), 3.43 (s, 2H).
The synthetic route of 1-Bromo-2,4,5-trifluorobenzene has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Chemo Iberica, S.A.; EP2423178; (2012); A1;,
Bromide – Wikipedia,
bromide – Wiktionary