Methyl bromoacetate → Methyl 3-{2-[(tert-butoxycarbonyl)amino]-4-pyridyl}propanoate

Temperature

-78 °C

tert-Butyl N-(4-methyl-2-pyridyl)carbamate (5 g, 24.0 mmol) was dissolved in tetrahydrofuran (120 ml), cooled to −78° C., and then added dropwise with n-butyl lithium (40 ml, 60 mmol). Then, the reaction solution was warmed and stirred at room temperature. The reaction mixture was stirred for 1 hour, then again cooled to −78° C., and added dropwise with methyl bromoacetate (3.4 ml) dissolved in tetrahydrofuran (10 ml). After the reaction mixture was stirred for 30 minutes, the reaction was stopped with saturated brine and the reaction mixture was extracted with ethyl acetate. The resulting organic layer was dried over sodium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform:ethyl acetate=3:1→5:1) to obtain 3.95 g (59%) of the title compound as pale yellow crystals.

1. temperatureThen, the reaction solution was warmed
2. stirringThe reaction mixture was stirred for 1 hour
3. temperatureagain cooled to −78° C.
4. stirringAfter the reaction mixture was stirred for 30 minutes
5. extractionthe reaction mixture was extracted with ethyl acetate
6. dry with materialThe resulting organic layer was dried over sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customthe residue was purified by silica gel column chromatography (chloroform:ethyl acetate=3:1→5:1)

ORD record

ord-83b9aa6d78b24a8f81eb1e5b13710333

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07056917B2