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

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°G, 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% ethyl-acetate/hexanes to give the desired product. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.55-1.69 (m, 1H), 1.91-2.05 (m, 1H), 2.19-2.28 (m, 2H), 2.46-2.55 (m, 2H), 5.59 (s, 1H), 7.33-7.40 (m, 2H), 7.44-7.48 (m, 2H).

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

ORD record

ord-1b32c7e6eaab4ef8ace2109e9011f8a7

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242139B2