Hydrochloric Acid → methyl 2-(4-bromo-2-methylphenyl)acetate

Temperature

130 °C

Potassium hydroxide (0.60 g, 11 mmol) was added to a solution of (4-bromo-2-methylphenyl)acetonitrile (1.0 g, 4.8 mmol) obtained in Example (17-1) in ethylene glycol (5 ml), and the mixture was stirred at 130° C. for 1.5 hours. After the reaction mixture was cooled to room temperature and concentrated hydrochloric acid was added to acidify the reaction mixture, the mixture was extracted with ethyl acetate. The organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. After the residue obtained by removing the solvent under reduced pressure was washed with water, it was dried under reduced pressure to give a solid. Potassium carbonate (0.97 g, 7.0 mmol) and methyl iodide (0.37 ml, 5.9 mmol) were added to a solution of the obtained solid in N,N-dimethylformamide (6 ml), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and the organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=99/1-10/1) to give crudely purified methyl (4-bromo-2-methylphenyl)acetate as an oil. According to a method similar to Example (8-1), from crude methyl (4-bromo-2-methylphenyl)acetate obtained in the above and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (814 mg, 3.7 mmol), methyl (4′-hydroxy-3-methyl-1,1′-biphenyl-4-yl)acetate was obtained as a colorless solid (0.70 g, three-step total yield: 56%).

1. temperatureAfter the reaction mixture was cooled to room temperature
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was successively washed with water
4. dry with materiala saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
5. customAfter the residue obtained
6. customby removing the solvent under reduced pressure
7. washwas washed with water, it
8. customwas dried under reduced pressure
9. customto give a solid
10. stirringthe mixture was stirred at room temperature for 2 hours
11. washthe organic layer was successively washed with water
12. dry with materiala saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
13. customThe residue obtained
14. customby removing the solvent under reduced pressure
15. customwas purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=99/1-10/1)

ORD record

ord-933876bab8f047079a482240991249c8

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07923573B2