Diisopropylamine → 1-(5-Bromo-2-fluoro-3-pyridinyl)-2-[4-(dimethylamino)phenyl]ethanone

Temperature

-20 °C

Diisopropylamine (1.93 ml, 13.66 mmol) and tetrahydrofuran (80 ml) were combined and cooled to −20° C. with stirring. n-Butyl lithium (2.5 M in hexanes, 5.2 ml, 13.00 mmol) was slowly added and stirred at this temperature for 30 minutes. The temperature was decreased to −78° C. and neat 5-bromo-2-fluoropyridine (1.34 ml, 13.02 mmol) was added (internal temperature was not allowed to exceed −68° C.). The reaction mixture was stirred at −78° C. for 40 minutes. The reaction mixture was added to a solution of 2-(4-dimethylamino-phenyl)-N-methoxy-N-methyl-acetamide (2.76 g, 12.42 mmol) in tetrahydrofuran (10 ml). The combined reaction mixture was stirred at −78° C. for 1 hour. The reaction mixture was slowly warmed to room temperature, and quenched with saturate aqueous ammonium chloride. The reaction mixture was extracted with methylene chloride, dried over sodium sulfate, and concentrated. The crude material was purified by flash chromatography (0 to 40% ethyl acetate in hexanes) to give 1.78 g (43%) of 1-(5-bromo-2-fluoro-pyridin-3-yl)-2-(4-dimethylamino-phenyl)-ethanone. MS m/z 337.1+339.1 (M+H+).

1. stirringstirred at this temperature for 30 minutes
2. customwas decreased to −78° C.
3. customto exceed −68° C.
4. stirringThe reaction mixture was stirred at −78° C. for 40 minutes
5. customThe combined reaction mixture
6. stirringwas stirred at −78° C. for 1 hour
7. temperatureThe reaction mixture was slowly warmed to room temperature
8. customquenched with saturate aqueous ammonium chloride
9. extractionThe reaction mixture was extracted with methylene chloride
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated
12. customThe crude material was purified by flash chromatography (0 to 40% ethyl acetate in hexanes)

ORD record

ord-316b1beac7c6486795ea07ad4b512a14

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268994B2