Hydrochloric Acid → (5-Bromo-2-methoxyphenyl)acetone

Temperature

75 °C

A mixture of 5-bromoanisaldehyde (19.4 g, 90 mmol), toluene (25 ml), nitroethane (8.1 g, 108 mmol) and butylamine (2.0 g, 27 mmol) was vigorously refluxed under heating while removing water generated by the reaction with a Dean-Stark distilling tube. During the reflux, N-butylamine (4.5 ml) and nitroethane (4 ml) were added in several portions and the reaction proceeded for 6 hr. Then, the reaction mixture was cooled and extracted with toluene and 3N hydrochloric acid. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure to give a brown oil containing 3-(2-nitropropen-1-yl)-4-methoxybromobenzene. The oil was dissolved in toluene (30 ml) and an aqueous solution (30 ml) of iron (III) chloride hexahydrate (1.0 g) was added. Thereto was added iron powder (15.1 g, 270 mmol) and the mixture was heated to 75° C. While vigorously stirring the mixture, concentrated hydrochloric acid (37.5 ml, 450 mmol) was dropwise added over 2 hr. After the dropwise addition, the mixture was stirred for 1 hr at 75° C. After cooling, the insoluble matter was filtered off and the filtrate was partitioned. The aqueous layer was extracted with toluene. The organic layers were combined, washed with 3N hydrochloric acid, and dried over anhydrous sodium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1) to give the objective compound (6.9 g, 33%) as a colorless oil.

1. temperaturewas vigorously refluxed
2. temperatureunder heating
3. customwhile removing water
4. customgenerated by the reaction with a Dean-Stark
5. distillationdistilling tube
6. additionDuring the reflux, N-butylamine (4.5 ml) and nitroethane (4 ml) were added in several portions
7. temperatureThen, the reaction mixture was cooled
8. extractionextracted with toluene and 3N hydrochloric acid
9. washThe organic layer was washed with saturated brine
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationThe desiccant was filtered off
12. concentrationthe filtrate was concentrated under reduced pressure
13. customto give a brown oil
14. additionwas dropwise added over 2 hr
15. additionAfter the dropwise addition
16. temperatureAfter cooling
17. filtrationthe insoluble matter was filtered off
18. customthe filtrate was partitioned
19. extractionThe aqueous layer was extracted with toluene
20. washwashed with 3N hydrochloric acid
21. dry with materialdried over anhydrous sodium sulfate
22. filtrationThe desiccant was filtered off
23. concentrationthe filtrate was concentrated under reduced pressure
24. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1)

ORD record

ord-16ee62ce28d94af3ada124e95c5f5475

Source dataset

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06911469B2