2-(Dimethylamino)ethanol → (6-Chloro-3-cyclopropylpyridin-2-yl)(2-fluoropyridin-3-yl)methanone

Temperature

-78 °C

A 2.5M solution of nBuLi (10.94 ml, 27.34 mmol) was added to a solution of 2-(dimethylamino)ethanol (1.37 ml, 13.67 mmol) in hexane (15 ml) cooled to −78° C. The reaction mixture was stirred at −78° C. for 30 minutes then, a solution of 2-chloro-5-cyclopropylpyridine (700 mg, 4.56 mmol) in hexane (10 mL) was added dropwise. The reaction mixture was stirred for 90 minutes. A solution of 2-fluoro-N-methoxy-N-methylnicotinamide (3.36 g, 18.23 mmol) in tetrahydrofuran (15 mL) was added dropwise and the reaction mixture was stirred at −78° C. for 1 hour. The reaction mixture was partitioned between a saturated solution of ammonium chloride and ethyl acetate. The organic extract was washed with a saturated solution of sodium bicarbonate and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography to afford the title compound as a colourless oil (1.14 g, 61% yield).

1. stirringThe reaction mixture was stirred for 90 minutes
2. stirringthe reaction mixture was stirred at −78° C. for 1 hour
3. customThe reaction mixture was partitioned between a saturated solution of ammonium chloride and ethyl acetate
4. extractionThe organic extract
5. washwas washed with a saturated solution of sodium bicarbonate and brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified on silica gel by flash column chromatography

ORD record

ord-5c43ba88801a46089e4a9e6d6f7fe43f

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08741931B2