Hydrochloric Acid → 3-Ethyl-4-[3-(4-trifluoromethoxyphenoxy)propyloxy]-5-methylphenol

Temperature

-70 °C

Then, 6.6 g of 4-bromo-2-ethyl-6-methyl-1-[3-(4-trifluoromethoxyphenoxy)propyloxy]benzene was dissolved in 200 ml of tetrahydrofuran, and the solution was stirred at -70° C., to which 9.6 ml of n-butyl lithium solution (in hexane, 1.58 mol/liter) was added dropwise, followed by further stirring at -70° C. for 2 hours. To this reaction mixture was added dropwise a solution of 2.2 g of triethoxy borane dissolved in 60 ml of tetrahydrofuran. Then, the reaction mixture was stirred for 1 hour, while warming to room temperature, and 13 ml of 10% aqueous hydrochloric acid solution was added in small portions, followed by stirring at room temperature for 20 minutes. The tetrahydrofuran layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated, to which 50 ml of toluene was added, and the mixture was heated at 70° C. under stirring, to which 6 ml of 30% aqueous hydrogen peroxide solution was added dropwise. The mixture was heated under reflux for 1 hour, and washed once with water, twice with 10% aqueous ammonium ferrous sulfate solution, and once with water. The toluene layer was dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 3.4 g of 3-ethyl-4-[3-(4-trifluoromethoxyphenoxy)propyloxy]-5-methylphenol (61% yield), nD25.4 1.4955.

1. additionwas added dropwise
2. stirringThen, the reaction mixture was stirred for 1 hour
3. temperaturewhile warming to room temperature
4. stirringby stirring at room temperature for 20 minutes
5. washThe tetrahydrofuran layer was washed with water
6. dry with materialdried with anhydrous magnesium sulfate
7. concentrationconcentrated, to which 50 ml of toluene
8. additionwas added
9. temperaturethe mixture was heated at 70° C.
10. stirringunder stirring, to which 6 ml of 30% aqueous hydrogen peroxide solution
11. additionwas added dropwise
12. temperatureThe mixture was heated
13. temperatureunder reflux for 1 hour
14. washwashed once with water, twice with 10% aqueous ammonium ferrous sulfate solution
15. dry with materialThe toluene layer was dried with anhydrous magnesium sulfate
16. concentrationconcentrated
17. customto obtain a crude product

ORD record

ord-7e978f3ee6e94eada2a91c16db7f11c0

Source dataset

uspto-grants-1999_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05872137