Diethyl Carbonate → Ethyl 2-(2-chloropyridin-4-yl)acetate

Temperature

-78 °C

In a 1000 mL round-bottom flask, diisopropylamine (80.21 mL, 567.5 mmol) was combined with THF (250 mL) and cooled to −78° C. Butyllithium (227.0 mL, 567.5 mmol) (2.5M in hexane) was added and the mixture was stirred for 30 minutes. 2-Chloro-4-methylpyridine (36.20 g, 283.8 mmol) in THF (100 mL) was added, and the mixture was stirred for 2 hours. A mixture of diethyl carbonate (37.82 mL, 312.1 mmol) and hexamethylphosphoramide (54.31 mL, 312.1 mmol) was added, and the mixture was stirred at −78° C. for one hour and then stirred at ambient temperature. The reaction was quenched with 25% ammonium chloride solution and extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried and evaporated. The crude oil was purified by silica gel chromatography, eluting with 5% ethyl acetate/hexane to provide the desired product as clear oil (42.75 g, 75.47% yield).

1. stirringthe mixture was stirred for 2 hours
2. additionwas added
3. stirringthe mixture was stirred at −78° C. for one hour
4. stirringstirred at ambient temperature
5. customThe reaction was quenched with 25% ammonium chloride solution
6. extractionextracted twice with ethyl acetate
7. washThe combined organic extracts were washed with brine
8. customdried
9. customevaporated
10. customThe crude oil was purified by silica gel chromatography
11. washeluting with 5% ethyl acetate/hexane

ORD record

ord-0996133c30114a7799e347736b3bccf5

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022222B2