Sodium hydride → HCID 18340730, compound

Temperature

80 °C

To a solution of tert-butyl cyanoacetate (10.0 g) in toluene (100 mL), sodium hydride (60% dispersion in mineral oil, 2.83 g) was added under cooling with ice. After being stirred at 80° C. for an hour, the mixture was cooled to 50° C. and methyl bromoacetate (6.51 mL) was added slowly. After adding tetrahydrofuran (15 mL), the mixture was stirred at 80° C. for two hours. The reaction mixture was cooled with ice and then sodium hydride (60% dispersion in mineral oil, 2.83 g) was added. After being stirred at 80° C. for an hour, the mixture was cooled to 50° C. and then methyl bromoacetate (6.51 mL) was added slowly. Subsequently, tetrahydrofuran (15 mL) was added and the mixture was stirred at 80° C. for two hours. After the reaction mixture to room temperature, a saturated aqueous solution of ammonium chloride and water were added and extraction was conducted with ethyl acetate. The combined organic layers were washed with water, a saturated aqueous solution of sodium hydrogen carbonate, and saturated brine successively and then dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0-40:60) to give 2-tert-butyl 1,3-dimethyl 2-cyanopropane-1,2,3-tricarboxylate as a pale yellow oil (17.8 g).

1. temperatureunder cooling with ice
2. temperaturethe mixture was cooled to 50° C.
3. stirringthe mixture was stirred at 80° C. for two hours
4. temperatureThe reaction mixture was cooled with ice
5. stirringAfter being stirred at 80° C. for an hour
6. temperaturethe mixture was cooled to 50° C.
7. stirringthe mixture was stirred at 80° C. for two hours
8. extractionextraction
9. washThe combined organic layers were washed with water
10. dry with materiala saturated aqueous solution of sodium hydrogen carbonate, and saturated brine successively and then dried over anhydrous magnesium sulfate
11. customThe desiccant was removed by filtration
12. concentrationthe filtrate was concentrated under reduced pressure
13. customThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0-40:60)

ORD record

ord-7556998724ba49768edcfbe781c77595

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09422240B2