1,2-Dibromoethane → 2-Bromo-3-methoxyphenol

33 mL (52.8 mMol) n-butyllithium (1.6 M in hexane) were added dropwise to a solution 10 gm (48.1 mMol) tetrahydropyran-2-yl 3-methoxyphenyl ether in 100 mL tetrahydrofuran over 15 minutes. After stirring for 2.5 hours at room temperature, the reaction mixture was cooled to 0° C. and then 4.6 mL (53.2 mMol) 1,2-dibromoethane were added dropwise. The reaction mixture was then allowed to stir at room temperature for about 14 hours. The reaction mixture was then diluted with 50 mL 1 N hydrochloric acid and was stirred for 1 hour. The aqueous phase was extracted with three 100 mL portions of diethyl ether. The organic phases were combined and extracted well with 5 N sodium hydroxide. These basic aqueous extracts were combined and cooled in an ice/water bath. The pH of this aqueous solution was adjusted to about 1 with 5 N hydrochloric acid and then extracted with three 100 mL portions of diethyl ether. These ether extracts were combined and washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography, eluting with a gradient of hexane containing from 0 to 10% ethyl acetate. Fractions containing the desired compound were combined and concentrated under reduced pressure to provide 2.91 gm (30%) of a residue which crystallized upon standing.

1. temperaturethe reaction mixture was cooled to 0° C.
2. stirringto stir at room temperature for about 14 hours
3. stirringwas stirred for 1 hour
4. extractionThe aqueous phase was extracted with three 100 mL portions of diethyl ether
5. extractionextracted well with 5 N sodium hydroxide
6. temperaturecooled in an ice/water bath
7. extractionextracted with three 100 mL portions of diethyl ether
8. washwashed with saturated aqueous sodium chloride
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. washeluting with a gradient of hexane containing from 0 to 10% ethyl acetate
12. additionFractions containing the desired compound
13. concentrationconcentrated under reduced pressure

ORD record

ord-e33f2c7ff9e74bf598596ee0d40a1e17

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881733B1