4-Ethoxybenzoic acid → (5-Bromo-2-chloro-6-methoxyphenyl)(4-ethoxyphenyl)methanone

A suspension of 2-bromo-5-chlorophenol (2.85 g, 13.7 mmol; synthesized in reference to International Patent Publication WO0109122), potassium carbonate (1.89 g, 13.7 mmol), n-Bu4NI (50 mg, 0.137 mmol), methyl iodide (1.28 mL, 20.6 mmol) and N,N-dimethylformamide (8.0 mL) was stirred for two hours. An iced water was added and the obtained mixture was extracted with ethyl acetate twice. The combined organic phase was washed with brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=95:5) to obtain colorless oily 2-bromo-5-chloroanisole (2.94 g, 97%). Then, oxalyl chloride (1.23 mL, 15.1 mmol) and N,N-dimethylformamide (2 drops) were added to 4-ethoxybenzoic acid (2.28 g, 13.7 mmol) in chloroform (8 mL) and stirred for five hours. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (5 mL). To this solution, a chloroform solution (10 mL) of 2-bromo-5-chloroanisole (2.94 g, 13.3 mmol) was added and then aluminum chloride (2.07 g, 15.5 mmol) was added portion wise at −10° C. over five minutes. After stirred at 5° C. for one hour, the reaction mixture was to room temperature and stirred for 13 hours. The reaction mixture was poured into an iced water and extracted with chloroform three times. After washed with 1 M hydrochloric acid, water, brine, the combined organic layer was dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by NH type silica gel column chromatography (hexane:ethyl acetate=9:1) to obtain (5-bromo-2-chloro-6-methoxyphenyl)(4-ethoxyphenyl)methanone (1.53 g, 31%) as a colorless crystal.

1. customThe yellow oil obtained
2. customby evaporating the solvent under reduced pressure
3. dissolutionwas dissolved in chloroform (5 mL)
4. stirringAfter stirred at 5° C. for one hour
5. customwas to room temperature
6. stirringstirred for 13 hours
7. extractionextracted with chloroform three times
8. washAfter washed with 1 M hydrochloric acid, water, brine
9. dry with materialthe combined organic layer was dried with anhydrous magnesium sulfate
10. filtrationAfter the desiccant was filtered off
11. customthe residue obtained
12. customby evaporating the solvent under reduced pressure
13. customwas purified by NH type silica gel column chromatography (hexane:ethyl acetate=9:1)

ORDレコード

ord-abd8ed39753444ec9236d8b3ca359240

出典データセット

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07910619B2