4-Chloro-3-methylphenol → 1-(5-Chloro-2-hydroxy-4-methylphenyl)propan-1-one

Temperature

60 °C

The 4-chloro-3-methyl-phenol (2 g, 10 mmol) and the propionyl chloride (1.8 mL, 20. mmol) were combined and the mixture was heated at 60° C. for 2 hours. The reaction was concentrated in vacuo to remove excess propionyl chloride to give an oil. To this was added aluminum trichloride (2.7 g, 20. mmol) and the mixture was heated at 180° C. for 30 minutes. The reaction mixture was then cooled to room temperature and slowly quenched with 1 N HCl while cooling in an ice bath. The reaction was partitioned between EtOAc and water. The organic layer was washed with 1 N HCl, water, brine, dried over magnesium sulfate and concentrated to give the crude product as a dark oil. The product was purified by chromatography on silica gel eluting with hexane:EtOAc gradient to give 1-(5-chloro-2-hydroxy-4-methylphenyl)propan-1-one as a solid (1.5 g, 60%). LCMS calculated for C10H12ClO2 (M+H)+: m/z=199.0. found: 198.9.

1. concentrationThe reaction was concentrated in vacuo
2. customto remove excess propionyl chloride
3. customto give an oil
4. temperaturethe mixture was heated at 180° C. for 30 minutes
5. temperatureThe reaction mixture was then cooled to room temperature
6. customslowly quenched with 1 N HCl
7. temperaturewhile cooling in an ice bath
8. customThe reaction was partitioned between EtOAc and water
9. washThe organic layer was washed with 1 N HCl, water, brine
10. dry with materialdried over magnesium sulfate
11. concentrationconcentrated
12. customto give the crude product as a dark oil
13. customThe product was purified by chromatography on silica gel eluting with hexane

ORD record

ord-e1a090c9ea654e8ea0430f481a7d6a51

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096600B2