Ethyl Acetate → Methyl 2-(3-cyanopyridin-4-YL)acetate

Temperature

-78 °C

1M LiHMDS (45 mL, 44.794 mmol) was added to a solution of 4-methylnicotinonitrile (2.52 g, 21.33 mmol) in THF (15 mL) at −78° C. and the resulting reaction mass was stirred at −78° C. for 1 hour. This was followed by the addition of dimethyl carbonate (1.98 mL, 23.464 mmol) and stirred the resulting reaction mass at −78° C. for 1 hour and further at 0° C. for 2 hours. The reaction was monitored by TLC (30% ethyl acetate in hexane). The reaction mass was quenched with saturated NH4Cl solution and extracted using ethyl acetate. The organic layer was washed with water, brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude product. Purification by column chromatography on silica gel (25% ethyl acetate in hexane) afforded 530 mg of the product (14.10% yield).

1. customthe resulting reaction mass
2. stirringstirred
3. customthe resulting reaction mass at −78° C. for 1 hour
4. waitfurther at 0° C. for 2 hours
5. customThe reaction mass was quenched with saturated NH4Cl solution
6. extractionextracted
7. washThe organic layer was washed with water, brine solution
8. dry with materialdried over anhydrous sodium sulphate
9. concentrationconcentrated under reduced pressure
10. customto afford the crude product
11. customPurification by column chromatography on silica gel (25% ethyl acetate in hexane)

ORD record

ord-c8226b0bd4364904b59fbcae2507c6e5

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946260B2