Water → HCID 58919970, compound

To a 50 mL flask flushed with nitrogen, equipped with a stir bar and cooled in a water bath was added potassium tertbutoxide (1.2 g, 11 mmol, 95%). DMSO was added (4 mL) followed by addition of a solution of 2,2,2-trifluoroethanol (1.1 g, 11 mmol) in DMSO (1 mL). The water bath was removed and 1-bromo-3,5-difluorobenzene (1.1 mL, 9.5 mmol) was added and the reaction mixture stirred at room temperature for 1 h. An additional portion of 2,2,2-trifluoroethanol was added (1.1 g, 11 mmol) and the reaction mixture stirred for 14 h. Additional potassium tertbutoxide (0.24 g, 2.2 mmol, 95%) was added followed by addition of a further aliquot of 2,2,2-trifluoroethanol (0.44 g, 4.4 mmol) and the resulting turbid solution stirred for 2 h. Water was added (200 mL), and the aqueous phase extracted with ether (1×200 mL). The organic portion was then washed successively with water (2×200 mL) and saturated NaCl solution (2×200 mL), dried over Na2SO4, decanted and concentrated under reduced pressure yielding a crude yellow liquid (2.1 g). A portion of the crude product (1.3 g) was purified by distillation under reduced pressure at 80° C. yielding 1-bromo-3-fluoro-5-(2,2,2-trifluoroethoxy)benzene as a colorless oil (0.70 g, 35% yield). 1H NMR (CDCl3, 400 MHz): 7.05 ppm (d, 1H), 6.90 ppm (s, 1H), 6.55 ppm (d, 1H), 4.32 ppm (q, 2H).

1. customTo a 50 mL flask flushed with nitrogen
2. customequipped with a stir bar
3. temperaturecooled in a water bath
4. customThe water bath was removed
5. stirringthe reaction mixture stirred for 14 h
6. stirringthe resulting turbid solution stirred for 2 h
7. extractionthe aqueous phase extracted with ether (1×200 mL)
8. washThe organic portion was then washed successively with water (2×200 mL) and saturated NaCl solution (2×200 mL)
9. dry with materialdried over Na2SO4
10. customdecanted
11. concentrationconcentrated under reduced pressure
12. customyielding a crude yellow liquid (2.1 g)
13. distillationA portion of the crude product (1.3 g) was purified by distillation under reduced pressure at 80° C.

ORD record

ord-ee2e99c242b149b5b4086a86958f7841

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07888376B2