Anisole → (5-Bromo-2-chlorothiophen-3-yl)(4-methoxyphenyl)methanone

To a solution of acid 1 (2.0 g, 8.28 mmol) in CH2Cl2 (50 mL) were added oxalyl chloride (0.87 mL, 9.94 mmol) and catalytic amounts of DMF at room temperature. The mixture was stirred at room temperature for 3 hours. The mixture was evaporated in vacuo and dried under high vacuum. The crude acid chloride was dissolved with CH2Cl2 (30 mL) and cooled to 0° C. To the mixture was added anisole (0.9 mL, 8.28 mmol) at 0° C. and stirred at 0° C. for 5 min. To the reaction mixture was added AlCl3 (1.2 g, 8.28 mmol) portionwise at 0° C. The mixture was stirred at 0° C. for 30 min, warmed up to room temperature and stirred at room temperature for 15 hours. The mixture was poured into ice-water and extracted with CH2Cl2 (50 mL×2). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica column chromatography (Biotage) to provide the title compound 2 (2.68 g, 98%).

1. customThe mixture was evaporated in vacuo
2. customdried under high vacuum
3. dissolutionThe crude acid chloride was dissolved with CH2Cl2 (30 mL)
4. temperaturecooled to 0° C
5. stirringstirred at 0° C. for 5 min
6. stirringThe mixture was stirred at 0° C. for 30 min
7. temperaturewarmed up to room temperature
8. stirringstirred at room temperature for 15 hours
9. extractionextracted with CH2Cl2 (50 mL×2)
10. dry with materialThe combined organic layer was dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified by silica column chromatography (Biotage)

ORD record

ord-6d2c319d464c4cd3936587810e464dd3

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006187B2