Hydrochloric Acid → 4-Benzyloxy-3-chloro-5-methylphenol

Temperatur

-70 °C

Then, 40 g of 4-bromo-6-chloro-2-methyl-1-benzyloxybenzene was dissolved in 400 ml of tetrahydrofuran, followed by stirring at -70° C., to which 76 ml of n-butyl lithium solution (in hexane, 1.69 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 13.3 g of trimethoxyborane dissolved in 50 ml of tetrahydrofuran. Then, the reaction mixture was stirred for 1 hours, while warming to room temperature, and 100 ml of 10% aqueous hydrochloric acid solution was added in small portions, followed by stirring for 20 minutes. The tetrahydrofuran layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated. The residue was mixed with 200 ml of toluene, and heated at 70° C. under stirring, to which 36 ml of 30% aqueous hydrogen peroxide solution was added dropwise. After heating under reflux for 1 hour, the reaction mixture was washed once with water, twice with 10% aqueous ammonium ferrous sulfate solution, and once with water, followed by phase separation. 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 29 g of 4-benzyloxy-3-chloro-5-methylphenol (91% yield).

1. additionwas added dropwise
2. stirringThen, the reaction mixture was stirred for 1 hours
3. temperaturewhile warming to room temperature
4. stirringby stirring for 20 minutes
5. washThe tetrahydrofuran layer was washed with water
6. dry with materialdried with anhydrous magnesium sulfate
7. concentrationconcentrated
8. additionThe residue was mixed with 200 ml of toluene
9. temperatureheated at 70° C.
10. stirringunder stirring, to which 36 ml of 30% aqueous hydrogen peroxide solution
11. additionwas added dropwise
12. temperatureAfter heating
13. temperatureunder reflux for 1 hour
14. washthe reaction mixture was washed once with water, twice with 10% aqueous ammonium ferrous sulfate solution
15. customonce with water, followed by phase separation
16. dry with materialThe toluene layer was dried with anhydrous magnesium sulfate
17. concentrationconcentrated
18. customto obtain a crude product

ORD-Eintrag

ord-d4cbc527999744898132ccbebf833200

Quelldatensatz

uspto-grants-1999_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05872137