Methyl iodide → 1-Bromo-2,4-difluoro-5-methoxybenzene

온도

0 °C

To a solution of 1,3 dibromo-4,6-difluorobenzene (10.0 g, 37 mmol) in THF (50 mL) at −20° C. was added isopropyl magnesium chloride (2.0M in THF, 42 mmol) and the resulting solution warm to 0° C. and stirred for 30 minutes. Trimethylborate (4.7 g, 45 mmol) was added and the mixture stirred at ambient temperature for 1 hour. The solution was recooled to −20° C. and peracetic acid (32%, 50 mmol) was added and the solution was stirred for 30 minutes at ambient temperature. The solution was then quenched with sodium bisulfite (5% solution, 75 mL) and then acidified with 6 N hydrochloric acid and extracted with ethyl ether (2×75 mL). Combined extracts were dried (sodium sulfate) and concentrated. The crude phenol was dissolved in acetonitrile (40 mL) and potassium carbonate (10 g, 74 mmol) and iodomethane (5.7 g, 40 mmol) were added and stirred at ambient temperature for 20 hours. The solution was concentrated and the residue taken into water (50 mL) and extracted with ethyl ether (2×75 mL) and the combined extracts were washed with brine, dried (sodium sulfate), and concentrated. The residue was purified by chromatography (hexanes) to give 1-bromo-2,4-difluoro-5-methoxybenzene (2.0 g, 8.6 mmol): LC/MS (m/z=223).

1. stirringthe mixture stirred at ambient temperature for 1 hour
2. customwas recooled to −20° C.
3. stirringthe solution was stirred for 30 minutes at ambient temperature
4. customThe solution was then quenched with sodium bisulfite (5% solution, 75 mL)
5. extractionextracted with ethyl ether (2×75 mL)
6. dry with materialCombined extracts were dried (sodium sulfate)
7. concentrationconcentrated
8. dissolutionThe crude phenol was dissolved in acetonitrile (40 mL)
9. stirringstirred at ambient temperature for 20 hours
10. concentrationThe solution was concentrated
11. extractionextracted with ethyl ether (2×75 mL)
12. washthe combined extracts were washed with brine
13. dry with materialdried (sodium sulfate)
14. concentrationconcentrated
15. customThe residue was purified by chromatography (hexanes)

ORD 기록

ord-c4361ce868eb4e1192e46ad2039e578f

출처 데이터셋

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07498468B2