Acetic Acid → Phenol, 5-bromo-2-fluoro-

Temperature

-20 °C

To a solution of 2,2,6,6-tetramethyl piperidine (5.6 mL, 33.2 mmol) in THF at −20° C. was added n-BuLi (1.6 M in hexanes, 18.8 mL, 30 mmol). The mixture was stirred at −20° C. for 10 min before it was cooled to −78° C. 1-Bromo-4-flurobenzene (2.95 mL, 27 mmol) was added over 10 min and the mixture was stirred at −78° C. for 2.0 h before trimethyl borate (6.0 mL, 54 mmol) was added. The mixture was stirred at −78° C. for 30 min and then at rt for 2.0 h. After it was cooled back to 0° C., glacial acetic acid (4.86 mL, 81 mmol) was added and stirred for 30 min, followed by addition of 30% H2O2 (4.86 mL, 81 mmol). The mixture was stirred at rt for 24 h, quenched by addition of MnO2 (40 mg). After stirring at rt for 30 min, the cloudy solution was filtered through a pad of wet Celite® and extracted with EtOAc. The EtOAc layer was washed with aquous NaHSO3, brine and dried over Na2SO4. The crude residue was purified by flash column chromatography (EtOAc:hexanes=1:5) to give 4.4 g (85%) of 23A as a liquid. 1H NMR (400 MHz, CDCl3) δ ppm 5.39 (s, 1H) 6.90-6.98 (m, 2H) 7.14 (dd, J=8.13, 1.98 Hz, 1H).

1. temperaturewas cooled to −78° C
2. additionwas added
3. stirringThe mixture was stirred at −78° C. for 30 min
4. waitat rt for 2.0 h
5. temperatureAfter it was cooled back to 0° C.
6. stirringstirred for 30 min
7. stirringThe mixture was stirred at rt for 24 h
8. customquenched by addition of MnO2 (40 mg)
9. stirringAfter stirring at rt for 30 min
10. filtrationthe cloudy solution was filtered through a pad of wet Celite®
11. extractionextracted with EtOAc
12. washThe EtOAc layer was washed with aquous NaHSO3, brine
13. dry with materialdried over Na2SO4
14. customThe crude residue was purified by flash column chromatography (EtOAc:hexanes=1:5)

ORD record

ord-d79a7db623f64d539c81decef14fd5ce

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622585B2