Thionyl Chloride → 1-Indanone, 4-bromo-

3-(2-Bromophenyl)propanoic acid (1) (550 g, 2.4 mol, 1 equiv) was dissolved in 1,2-dichloroethane (5.5 L). Thionyl chloride (437.8 mL, 6 mol, 2.5 equiv) was added to the solution and the mixture was refluxed for 24 hours. The reaction was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in methylene chloride (1 L) and added dropwise to a mechanically stirred suspension of anhydrous aluminum chloride (526.9 g, 3.96 mol, 1.65 equiv) in dichloromethane (1 L) while keeping the reaction temperature below 27° C. The reaction was stirred at room temperature for three hours before being quenched into a five gallon bucket which was half-full of ice. The resulting mixture was extracted with dichloromethane (3×3 L). The combined organic layers were washed sequentially with saturated brine (2 L) and saturated sodium bicarbonate (2 L). The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The resulting solid was dried overnight in a vacuum oven at 30° C. to give compound 2 (435 g, 86% yield) as an off-white solid.

1. temperaturethe mixture was refluxed for 24 hours
2. concentrationconcentrated under reduced pressure
3. dissolutionThe residue was dissolved in methylene chloride (1 L)
4. customthe reaction temperature below 27° C
5. custombefore being quenched into a five gallon bucket which
6. extractionThe resulting mixture was extracted with dichloromethane (3×3 L)
7. washThe combined organic layers were washed sequentially with saturated brine (2 L) and saturated sodium bicarbonate (2 L)
8. dry with materialThe organic layer was dried over sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe resulting solid was dried overnight in a vacuum oven at 30° C.

ORD record

ord-d4f2569d2b0f414b89331a78fda2f002

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249239B2