5-Bromo-2,4-dichloropyrimidine → (2,4-Dichloro-pyrimidin-5-yl)-(2-methylsulfanyl-pyrimidin-4-yl)-methanol

Temperature

0 °C

To a stirred solution of 5-bromo-2,4-dichloropyrimidine (14.83 g, 65 mmol) in THF (200 mL) was added isopropylmagnesium chloride (78 mL, 1M, 78 mmol) dropwise at −30° C. After 30 minutes, 2-(methylthio)pyrimidine-4-carbaldehyde (10 g, 65 mmol) was added to the mixture. The mixture was warmed to 0° C. and stirred for 1 hour. Then the reaction mixture was quenched with saturated ammonium chloride solution (20 mL) and extracted with ethyl acetate (200 mL). The filtrate was washed with water (3×25 mL), brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by column chromatography (silica, 20 g, 200-300 mesh, eluting with methanol:dichloromethane, 1:50) to afford (2,4-dichloro-pyrimidin-5-yl)-(2-methylsulfanyl-pyrimidin-4-yl)-methanol. (Yield 13.85 g, 71%).

1. customThen the reaction mixture was quenched with saturated ammonium chloride solution (20 mL)
2. extractionextracted with ethyl acetate (200 mL)
3. washThe filtrate was washed with water (3×25 mL), brine (25 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated to dryness
7. customThe residue was purified by column chromatography (silica, 20 g, 200-300 mesh, eluting with methanol:dichloromethane, 1:50)

ORD record

ord-f8eebbdfacd04556b4b1c565130abff4

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362023B2