Propanal → HCID 21946018, compound

Temperature

-78 °C

Diisopropylamine (1.10 mL; 7.85 mmol) (Aldrich) was dissolved in freshly distilled tetrahydrofuran (15 mL) and cooled to −78° C. n-Butyllithium (2.5 M in hexanes, 3.10 mL; 7.75 mmol) (Aldrich) was added dropwise and stirring continued for 30 minutes to give a LDA solution. A solution of 2,4-dichloropyrimidine (0.50 g; 3.36 mmol) (Aldrich) in tetrahydrofuran (3 mL) was added to this freshly prepared LDA solution over 12 minutes. After 30 minutes stirring at −78° C., propionaldehyde (0.48 mL; 6.65 mmol) (Aldrich) was added over 6 minutes and stirring continued for another 35 minutes. The reaction was quenched with the addition of 25% aqueous ammonium chloride solution (15 mL) and was then diluted with ethyl acetate and water. The organic phase was washed with a second portion of ammonium chloride solution and then brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash chromatography (Biotage; 40M; 15:85 to 25:75 ethyl acetate-hexanes gradient) to give (±)-1-(2,4-dichloro-pyrimidin-5-yl)-propan-1-ol. (Yield 0.260 g; 37%).

1. stirringstirring
2. waitcontinued for another 35 minutes
3. customThe reaction was quenched with the addition of 25% aqueous ammonium chloride solution (15 mL)
4. additionwas then diluted with ethyl acetate and water
5. washThe organic phase was washed with a second portion of ammonium chloride solution
6. dry with materialbrine, dried over anhydrous sodium sulfate
7. concentrationconcentrated
8. customThe residue was purified by flash chromatography (Biotage; 40M; 15:85 to 25:75 ethyl acetate-hexanes gradient)

ORD record

ord-e5c64cfe25d447ec92dab68f4e739924

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07112676B2