Peracetic Acid → 5-(1-Bromoethyl)-2-fluoropyridine

Temperatur

0 °C

Thionyl bromide (11.60 mL, 149 mmol) was added (dropwise over 15 min; gas evolution) to a solution of 1-(6-fluoropyridin-3-yl)ethanol (10.55 g, 74.7 mmol) in DCM (300 mL) at 25° C., and the resulting orange solution was stirred at 25° C. for 3 h. Excess SOBr2 was then carefully quenched with water (150 mL) at 0° C. with vigorous stirring, and 5.0N aqueous NaOH (100 mL) was then carefully added at 0° C. (over about 10 min) to neutralize HBr and SO2. (Yellow mixture results; final pH about 9; adjust with saturated aqueous NaHCO3,to a pH of about 9 as necessary.) The resulting mixture was vigorously stirred at 0° C. for 5 min to ensure complete quench of acidic species, and the resulting mixture was then partitioned between DCM (200 mL) and half saturated aqueous NaHCO3 to a pH of about 9 (600 mL). The organic layer was separated, and the aqueous layer was extracted with DCM (300 mL). The combined organic extracts were sequentially washed with saturated aqueous NaHCO3 (500 mL) and brine (500 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to provide 5-(1-bromoethyl)-2-fluoropyridine (14.58 g, 96% yield) as a yellow oil (71% LCAP; m/z (ESI, +ve) 204.0 (M+H)+), which was used directly in Step 3.

1. customExcess SOBr2 was then carefully quenched with water (150 mL) at 0° C. with vigorous stirring, and 5.0N aqueous NaOH (100 mL)
2. additionwas then carefully added at 0° C. (over about 10 min)
3. custom(Yellow mixture results
4. customto ensure complete quench of acidic species
5. customthe resulting mixture was then partitioned between DCM (200 mL) and half saturated aqueous NaHCO3 to a pH of about 9 (600 mL)
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted with DCM (300 mL)
8. washThe combined organic extracts were sequentially washed with saturated aqueous NaHCO3 (500 mL) and brine (500 mL)
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD-Eintrag

ord-0e9b1d96b9084d3fb1385a81fb78aaf7

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08772480B2