Ammonium Chloride → 2-[1-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-propyl]-malonic acid diethyl ester

Temperature

-78 °C

To a stirred suspension of copper iodide (5.71 g, 30 mmol) in diethyl ether (120 mL) under argon was added ethylmagnesium bromide (3 M solution in diethyl ether, 20 mL, 20 mmol) within 10 min at 0° C. After 5 min stirring the mixture was cooled to −78° C. and a solution of 2-(6tert-butoxycarbonylamino-pyridin-3-ylmethylene)-malonic acid diethyl ester (5.47 g, 15.0 mmol) in tetrahydrofurane (60 mL) was added dropwise with in 0.5 h. During this period tetrahydrofurane (40 mL) was added. The mixture was allowed to stir at −40° C. for 2.5 h. Then a solution of ammonium chloride (5%) in aqueous ammonia solution (5%) was added with vigorous stirring, allowing access of air, and the mixture was warmed up to room temperature. The mixture was extracted twice with ethyl acetate. The combined organic layers were washed successively with aqueous ammonia solution (5%) and brine, and dried over magnesium sulphate. The solvent was removed under reduced pressure and the residue was recrystallised from a mixture of diisopropyl ether and tetrahydrofurane (5:1, vol./vol.) to give 2-[1-(6-tert-butoxycarbonylamino-pyridin-3-yl)-propyl]-malonic acid diethyl ester (3.23 g, 55%).

1. stirringto stir at −40° C. for 2.5 h
2. temperaturethe mixture was warmed up to room temperature
3. extractionThe mixture was extracted twice with ethyl acetate
4. washThe combined organic layers were washed successively with aqueous ammonia solution (5%) and brine
5. dry with materialdried over magnesium sulphate
6. customThe solvent was removed under reduced pressure
7. customthe residue was recrystallised from a mixture of diisopropyl ether and tetrahydrofurane (5:1

ORD record

ord-2038decc37924e4b995807afaba5bba6

Source dataset

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07071175B1