2,4-Dichloropyrimidine → 2-Chloro-4-cyclobutylpyrimidine

Temperature

-78 °C

2,4-Dichloropyrimidine (250 mg, 1.68 mmol) and ferric acetylacetonate (30 mg, 0.08 mmol) were taken up in tetrahydrofuran (3.4 ml) and the reaction was cooled to −78° C. Cyclobutylmagnesium chloride (3.4 ml of 0.5 M, 1.68 mmol) was added dropwise and the mixture was stirred at −78° C. for 30 min. The mixture was quenched with aqueous ammonium chloride and extracted with ethyl acetate. The combined organic fractions were washed with aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by Combiflash (0-5% ethyl acetate in hexanes) to provide 121 mg (0.72 mmol, 43%) of 2-chloro-4-cyclobutylpyrimidine as a colorless oil. MS APCI: [M+H]+ m/z 169.1. Step 2:

1. customThe mixture was quenched with aqueous ammonium chloride
2. extractionextracted with ethyl acetate
3. washThe combined organic fractions were washed with aqueous sodium hydrogen carbonate
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. customthe solvent was evaporated under reduced pressure
7. customThe residue was purified by Combiflash (0-5% ethyl acetate in hexanes)

ORD record

ord-42377fe43c924ccfacfeb1625ef731cd

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735417B2