Cyclohexanol → 1-Bromo-5-chloro-4-(cyclohexyloxymethyl)-2-fluorobenzene

To a solution of (4-bromo-2-chloro-5-fluorophenyl)methanol (5.00 g, 21.00 mmol) in dichloromethane (150 mL) was added phosphorous tribromide (8.53 g, 31.50 mmol) at 0° C. The clear reaction solution was stirred at the same temperature for 1 hour, then at an ambient temperature for 2 hours. The reaction mixture was concentrated in vacuo to dryness to obtain viscous yellow liquid which was added to a stirred mixture of cyclohexanol (1.68 g, 16.80 mmol) and sodium hydride (60% dispersion in mineral oil, 1.93 g, 21.00 mmol,) in N,N-dimethylformamide (15 mL) at 0° C. The reaction mixture was stirred at ambient temperature for 16 hours and quenched with addition of saturated ammonium chloride (100 mL). The organic layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over anhydrous sodium sulfate and filtered the solid. The filtrate was concentrated in vacuo to dryness. The residue was purified by flash column chromatography with ethyl acetate in hexanes (10%) to afford the title compound (2.60 g, 38%) as a viscous liquid: MS (ES+) m/z 320.9, 318.9 (M+1).

1. waitat an ambient temperature for 2 hours
2. concentrationThe reaction mixture was concentrated in vacuo to dryness
3. customto obtain viscous yellow liquid which
4. stirringThe reaction mixture was stirred at ambient temperature for 16 hours
5. customquenched with addition of saturated ammonium chloride (100 mL)
6. extractionThe organic layer was extracted with ethyl acetate (3×50 mL)
7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
8. filtrationfiltered the solid
9. concentrationThe filtrate was concentrated in vacuo to dryness
10. customThe residue was purified by flash column chromatography with ethyl acetate in hexanes (10%)

ORD record

ord-b5132a9c24ec4cf6add494858ec06c96

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2