4-Bromo-2-fluorophenol → 1-(3-Fluoro-4-hydroxyphenyl)propan-1-one

Temperature

-78 °C

A mixture of 4-bromo-2-fluorophenol (1.0 g, 5.24 mmol) in tetrahydrofuran (15 mL) was chilled to −78° C. and butyllithium (4.6 mL, 11.5 mmol, 2.5 M solution) was added rapidly, dropwise. The reaction was stirred 12 min and N-methyl-N-methoxypropionamide (the compound of Preparation 9, 0.735 g, 6.28 mmol in 1 mL of tetrahydrofuran with a 1 mL rinse) was added. The reaction was allowed to stir 5 min at −78° C. and then it was warmed to ambient temperature. A few drops of water were added; then the solvent was removed at reduced pressure. The residue was taken up in methylene chloride and washed with aqueous ammonium chloride and brine. The organic layer was dried and concentrated. The residue was flash chromatographed on silica gel (1×2.5 inches packed in hexane) with elution proceeding as follows: 10% ethyl acetate/hexane (250 mL), discarded forerun; 20% ethyl acetate/hexane (250 mL), 0.186 g of a yellow crystalline solid which had NMR identical to that of preparation 7.

1. washrinse)
2. additionwas added
3. stirringto stir 5 min at −78° C.
4. temperatureit was warmed to ambient temperature
5. additionA few drops of water were added
6. customthen the solvent was removed at reduced pressure
7. washwashed with aqueous ammonium chloride and brine
8. customThe organic layer was dried
9. concentrationconcentrated
10. customchromatographed on silica gel (1×2.5 inches packed in hexane) with elution proceeding
11. customof preparation 7

ORD record

ord-d3b3aa1b9bfd49ebbc424b62efb1134f

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06258827B1