Methylamine → N-(2-Ethoxycarbonyl-ethyl)-N-methyl-malonamic acid ethyl ester

Temperature

0 °C

To a cold (0° C.) solution of methylamine in ethanol (400 mL; 33% wt), ethyl acrylate (39.7 g, 0.397 mol) was added over a period of 20 minutes. The reaction mixture was stirred at 0° C. for 2 hours, and concentrated under vacuum. The crude product was used without further purification. The above crude product (21.8 g, 0.166 mol), diisopropylethylamine (28.9 mL, 0.166 mol), and 4-(N,N-dimethylamino)pyridine (2 g, 16 mmol) was dissolved in dichloromethane (300 mL) and cooled to 0° C. The mixture was treated with ethyl 3-chloro-3-oxopropionate (21.3 mL, 0.166 mol) and stirred at 0° C. for one hour. The mixture was allowed to warm up to room temperature and stirred overnight. The reaction mixture was partitioned with aq HCl (400 mL, 1M). The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide the title compound as yellow oil

1. concentrationconcentrated under vacuum
2. customThe crude product was used without further purification
3. temperaturecooled to 0° C
4. stirringstirred at 0° C. for one hour
5. temperatureto warm up to room temperature
6. stirringstirred overnight
7. customThe reaction mixture was partitioned with aq HCl (400 mL, 1M)
8. extractionThe organic extract
9. washwas washed with brine
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated under vacuum

ORD record

ord-6fbcb1cec3c04e84979e9b9c29310c06

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07435735B2