Cyclobutanone → 1-(4-Bromo-2-fluorophenyl)cyclobutanol

Temperature

-78 °C

A 100 mL 3-neck round bottom flask was charged with 4-bromo-2-fluoro-1-iodobenzene (1000 mg, 3.32 mmol) and diethyl ether (30 mL). The solution was cooled to −78 °C., and n-butyllithium (1.329 mL, 3.32 mmol) was added dropwise, keeping the temperature below −68° C. After stirring for 15 min, cyclobutanone (0.249 mL, 3.32 mmol) was added dropwise, keeping temperature; below −68° C. The solution was stirred at −78° C. for 15 min. The reaction was then quenched by the addition of saturated ammonium chloride (25 mL). The layers were separated, and the organic was washed with water (1×10 mL) and brine (1×10 mL). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue Was purified by flash chromatography (SiO2 gel), eluting with 3% ethylacetate/hexanes to give the desired product. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.55-1.69 (m, 1 H), 1.91-2.05 (m, 1 H), 2.19-2.28 (m, 2 H), 2.46-2.55 (m, 2 H), 5.59 (s, 1 H), 7.33-7.40 (m, 2 H), 7.44-7.48 (m, 2 H).

1. customthe temperature below −68° C
2. custombelow −68° C
3. stirringThe solution was stirred at −78° C. for 15 min
4. customThe reaction was then quenched by the addition of saturated ammonium chloride (25 mL)
5. customThe layers were separated
6. washthe organic was washed with water (1×10 mL) and brine (1×10 mL)
7. dry with materialThe organic layer was dried with anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue Was purified by flash chromatography (SiO2 gel)
10. washeluting with 3% ethylacetate/hexanes

ORD record

ord-d0af6007163043369ff9167eec713dd7

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901152B2