Sodium hydride → Dimethyl 4-fluoro-2-nitrophenylmalonate

Sodium hydride (2.6 g) and 14.5 g of dimethylmalonate was stirred and heated to 100° C. in 160 mL dimethylsulfoxide for 1.0 hour. The mixture was cooled to room temperature, 7.95 g of 2,5-difluoronitrobenzene were added and mixture stirred for 30 minutes. The mixture was then heated to 100° C. for 1.0 hour, cooled to room temperature and poured into 400 mL of saturated ammonium chloride solution. The mixture was extracted with 200 mL of ethyl acetate and the organic layer washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was crystallized from methanol to give 24.4 g (80% yield) of dimethyl 4-fluoro-2-nitrophenylmalonate as a white solid, Rf 0.2 on thin layer chromatography (ethyl acetate:hexane 1:6, silica gel). The filtrate was concentrated and chromatographed on a column of silica gel (ethyl acetate:hexane 1:8) to give an additional 5.03 g of dimethyl 4-fluoro-2-nitrophenylmalonate, for a total of 29.5 g (96% yield).

1. temperatureThe mixture was then heated to 100° C. for 1.0 hour
2. temperaturecooled to room temperature
3. extractionThe mixture was extracted with 200 mL of ethyl acetate
4. washthe organic layer washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under vacuum
7. customThe residue was crystallized from methanol

ORD record

ord-98435986c7b44f1aa5cf5a4e385d7145

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06313158B1