Introduction of a new synthetic route about 875664-38-3

The synthetic route of 875664-38-3 has been constantly updated, and we look forward to future research findings.

875664-38-3, name is 1-Bromo-4,5-difluoro-2-methylbenzene, belongs to bromides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Application In Synthesis of 1-Bromo-4,5-difluoro-2-methylbenzene

4′,5′-Difluoro-2′-methyl-biphenyl-4-ol To a stirred solution of 3,4-difluorotoluene (30 g, 234.1 mmol) and iron powder (0.784 g, 14.05 mmol) in methylene chloride (140 mL) in an ice bath was added bromine (12 mL, 155 mmol) slowly over 6.5 hrs. The reaction mixture was warmed to RT and stirred for an additional 60 hrs. The mixture was washed with water (200 mL), 10% Na2SO3 (3*150 mL), saturated (NaHCO3 (100 mL) and saturated NaCl. The organic layer was dried over MgSO4, filtered and concentrated in vacuo to give 40 g of crude 1-bromo-4,5-difluoro-2-methyl-benzene. Bromo-4,5-difluoro-2-methyl-benzene (30 g, 145 mmol) and 4-hydroxyphenyl-boronic acid (20.99 g, 152.2 mmol) were suspended in 725 ml of dioxane. The mixture was degassed with argon. Potassium carbonate (23.17 g, 166 mmol) in 72.5 ml water solution was added and after stirring for 10 minutes, bis(tricyclohexylphosphine)palladium(0) (2.4 g, 3.62 mmol) was added. The reaction was stirred at 80-85 C. for 19 hrs and concentrated. The mixture was diluted with ethyl acetate and water. The organic layer was washed with brine, dried and solvents were evaporated. The crude product was purified by flash chromatography, eluting with 0-7% ethyl acetate in hexanes to obtain the crude product which was further recrystallized from hexane to afford 4′,5′-difluoro-2′-methyl-biphenyl-4-ol (23.76 g, 74.5%). LR-MS (ES) calculated for C13H10F2O, 220.22. found m/z 219 [M-H].

The synthetic route of 875664-38-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bolin, David Robert; Hamilton, Matthew Michael; McDermott, Lee Apostle; Qian, Yimin; US2011/112158; (2011); A1;,
Bromide – Wikipedia,
bromide – Wiktionary