Diisopropylamine → Ethyl 4,6-dichloro-2-(methylsulfanyl)pyrimidine-5-carboxylate

Temperature

0 °C

Under an argon atmosphere, to a solution of diisopropylamine (15.7 mL, 112 mmol) in THF (70 mL) was added dropwise butyllithium (1.6M hexane solution, 70 mL, 112 mmol) at −78° C. The mixture was stirred at 0° C. for 30 min and cooled to −78° C. A solution of 4,6-dichloro-2-(methylsulfanyl)pyrimidine (14.12 g, 72.4 mmol) in THF (20 mL) was added dropwise thereto, and the mixture was stirred at −78° C. for 1 hr. A solution of ethyl chlorocarbonate (13.9 mL, 145 mmol) in THF (20 ml) was added dropwise thereto, and the mixture was stirred at −78° C. for 30 min, and then at 0° C. for 30 min. Water was added thereto, and the mixture was extracted twice with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluate, hexane:ethyl acetate=100:0→90:10) to give the title compound (13.28 g, 69%) as a colorless solid.

1. temperaturecooled to −78° C
2. stirringthe mixture was stirred at −78° C. for 1 hr
3. stirringthe mixture was stirred at −78° C. for 30 min
4. waitat 0° C. for 30 min
5. extractionthe mixture was extracted twice with ethyl acetate
6. washThe extract was washed with brine
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (eluate, hexane:ethyl acetate=100:0→90:10)

ORD record

ord-5f838be4a5e249b989261f58ada63831

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614208B2