A new synthetic route of 2-Chloro-5-(trifluoromethyl)benzyl alcohol

At the same time, in my other blogs, there are other synthetic methods of this type of compound,64372-62-9, 2-Chloro-5-(trifluoromethyl)benzyl alcohol, and friends who are interested can also refer to it.

With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.64372-62-9, name is 2-Chloro-5-(trifluoromethyl)benzyl alcohol, molecular formula is C8H6ClF3O, molecular weight is 210.58, as common compound, the synthetic route is as follows.Safety of 2-Chloro-5-(trifluoromethyl)benzyl alcohol

Step 1 : Suzuki Coupling Reaction of Boronic Acid 5 and Aryl Chloride 13 to yield 6: A 3 M K2CO3 solution is prepared by adding 4.71 kg of solid K2CO3 to 10.3 L water. Cooling is applied to keep the solution at 20-25 0C. THF (12 L), aryl chloride 13 (2.69 kg), and boronic acid 5 (2.74kg) are added to the K2CO3 followed by a 1 L THF rinse. HPLC analysis is used to confirm the 1.00/1.00 ratio of 5/13. The solution is degassed by sparging with nitrogen gas for 70 min. The catalyst, 1,1 bis(di-tert- butylphosphino)ferrocene palladium dichloride (42g) is added as a solid and is followed by a degassed THF rinse (1.5 L). The organic layer turns dark brown immediately. The biphasic mixture is aged at 36-40C with vigorous stirring. After HPLC reveals complete conversion (15-18 h), the mixture is cooled to rt and the aqueous layer is removed. To the organic layer is added heptane (25.6L) and water (25.6 L) and the layers are cut. The organic layer is washed with water (19L). The organic layer is treated with 680 g Darco KB-B at rt for 60 min and filtered through solka-floc with a 10%THF/Heptane rinse (-15 L). The solvent is switched to heptane (-35 L) at -45-50 0C until <0.5v% of THF is left. More heptane is added to bring the total volume to -45-50 L. The solution is seeded with crystals obtained from earlier runs if no seed bed forms. The slurry is slowly cooled to rt and then to -15 0C. After aging at -15 0C for 1-2 h, after LC of the supernatant shows that there will be ~2g/l loss of the product in the supernatant, the slurry is filtered and the product is washed with cold heptane (-25 L), providing compound 6. At the same time, in my other blogs, there are other synthetic methods of this type of compound,64372-62-9, 2-Chloro-5-(trifluoromethyl)benzyl alcohol, and friends who are interested can also refer to it. Reference:
Patent; MERCK & CO., INC.; WO2007/5572; (2007); A1;,
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