432-21-3, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 432-21-3 as follows.
1-Chloro-3-iodo-2trifluoromethyl-benzene; To a suspension of 3-Chloro-2-trifluoromethyl-phenylamine (121.61 g, 0.622 mol) in water (356 mL) was added 37% aqueous HCl portionwise allowing reaction temperature to rise to 42 C. The mixture was stirred for 30 minutes then cooled with ice/MeOH bath to 5 C. DCM (40 mL) was added and the mixture was stirred for 10 minutes. A solution of NaNO2 (53.52 g, 0.776 mol) in water (99 mL) was added dropwise while keeping the temperature of the reaction mixture below 5 C. After complete addition, the reaction mixture was stirred for 30 minutes and a solution of NaI (110.98 g, 0.740 mol) in water (198 mL) was added dropwise while keeping the temperature of the reaction mixture below 5 C. After completion of the addition, the reaction mixture was stirred for 1 hour and 15 minutes, and DCM (0.79 L) was added followed by NaHSO3(35.92 g) to discharge iodine color. The organic layer was washed (brine), and the water layer was sequentially reextracted (2¡Á0.2 L DCM). The organic layers were dried (Na2SO4), combined, and the volatiles were evaporated. The residue (180.55 g) was purified on 0.8 kg of silica gel (elution with 4 L of cyclohexane). The fractions were analyzed by GC, and those having more than 80% of the product were combined, and the volatiles were evaporated. The liquid residue was placed in the freezer for 1 hour, after which the solids were filtered, washed (pentane) and air-dried to afford 78.84 g (41%) of the desired product as beige solid in several crops (97-98% GC purity with 1H and 19F NMR’s clean and consistent with the desired product). The mother liquors were purified on 0.8 kg of silica gel (eluting with 4 L of cyclohexane). The fractions were analyzed by GC, and those having more than 80% of the product were combined and the volatiles were evaporated. The liquid residue was placed in the freezer for 1 hour, and solids were filtered, washed (pentane), and air-dried to give an additional 31.56 g (17%) of the 1-Chloro-3-iodo-2-trifluoromethyl-benzene as white solid (96% GC purity with 1H and 19F NMR’s clean and consistent with the desired product). Also, additional product was obtained (14.30 g, 8%, 81% pure GC) from mother liquors and 28.82 g (50% by GC, froim the less pure fractions. GC analysis done on a DB5 Column, 30 meters, 0.32 mm id, 0.25 um film, 75-300 C., 15 C./min., Injector temperature: 275 C., Detector temperature: 350 C., Retention time: 3.88 minutes. MS: APCl: M+: 306.0 (305.9)
At the same time, in my other blogs, there are other synthetic methods of this type of compound, 432-21-3, and friends who are interested can also refer to it.
Reference:
Patent; Pfizer Inc.; US2008/167319; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics