Hexane → 2-(Allyloxy)-1-(5-bromo-2-fluorophenyl)ethanone

Temperature

-72 °C

To a stirred −72° C. solution of 4-bromo-1-fluoro-2-iodobenzene (130.4 g, 433.5 mmol) in tetrahydrofuran (722 mL) is added 2.5 M butyl lithium in hexane (173.4 mL, 433.5 mmol) under a nitrogen atmosphere over 40 min. The reaction is stirred for 30 minutes at −72° C. and 2-(allyloxy)-N-methoxy-N-methylacetamide (57.5 g, 361.2 mmol) in tetrahydrofuran (115 mL) is added dropwise for 35 minutes. After 45 min at −72° C., the cooling bath is removed and mixture is warmed to 25° C. The reaction is quenched with saturated aqueous NH4Cl (500 mL), diluted with water (300 mL) and extracted three times with ethyl acetate. Organics are combined, dried over magnesium sulfate, filtered, and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using a linear gradient of 5% to 10% ethyl acetate in hexanes to give the title compound (63 g, 64%). ES/MS m/e (79Br/81Br) 273/275 (M+1).

1. waitAfter 45 min at −72° C.
2. customthe cooling bath is removed
3. temperaturemixture is warmed to 25° C
4. customThe reaction is quenched with saturated aqueous NH4Cl (500 mL)
5. additiondiluted with water (300 mL)
6. extractionextracted three times with ethyl acetate
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. customthe solvent is removed under reduced pressure
10. customThe residue is purified by silica gel chromatography

ORD record

ord-f55f568cc70a41188f64f10d7465fed9

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278441B2