Potassium Carbonate → 1-Bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene

Temperature

70 °C

To a solution of 3-bromo-5-fluorophenol (104 mmol crude), prepared as described in Step 1, Procedure 7, and iodo-1,1,2,2,-tetrafluoroethane (28.4 g, 125 mmol) in DMSO (80 mL) was added K2CO3 (57.0 g, 420 mmol). The reaction mixture was sealed in a thick walled glass pressure round bottom flask and heated at 70° C. for 18 h. The reaction mixture was cooled to rt, diluted with water (500 mL) and extracted with ether (3×200 mL). The combined ether layers were washed with 1N NaOH (2×200 mL), water (2×200 mL) and sat. NaCl (200 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to yield a residue. The residue was dissolved in ether (150 mL) and filtered through a plug of activated basic alumina. The filtrate was concentrated under reduced pressure to give 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene as a pale yellow oil (27.2 g, 88% for two steps) which was used without further purification. LCMS: RT=1.91 min, [M+H] No Ionizable peak (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); HPLC: RT=3.76 min (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.2% PPA; 4 mL/min, monitoring at 220 nm, Purity 100%); NMR: 400 MHz 1H (CDCl3) ppm 7.19 (m, 2 H), 6.92 (d, J=8.35Hz, 1 H), 5.88 (tt; J=52.95 Hz and J=2.64 Hz, 1 H).

1. customThe reaction mixture was sealed in a thick walled glass pressure round bottom flask
2. temperatureThe reaction mixture was cooled to rt
3. extractionextracted with ether (3×200 mL)
4. washThe combined ether layers were washed with 1N NaOH (2×200 mL), water (2×200 mL) and sat. NaCl (200 mL)
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto yield a residue
9. filtrationfiltered through a plug of activated basic alumina
10. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-8503cab782d341ea81b3cf8f98f436b6

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404896B2