Dimethyl malonate → Dimethyl 2-(2-fluoro-4-nitrophenyl)malonate

Temperature

100 °C

9.13 g (69.1 mmol) of dimethyl malonate are carefully added dropwise to a suspension of 1.66 g (69.1 mmol) of washed sodium hydride in 70 ml of DMSO. The mixture is heated at 100° C. for 40 min and then cooled to RT, and 5.00 g (31.4 mmol) of 3,4-difluoronitrobenzene are added. The mixture is stirred at RT for 30 min and then heated at 100° C. for one hour. The cooled reaction mixture is poured into a mixture of ethyl acetate (50 ml), cyclohexane (50 ml) and saturated ammonium chloride solution (250 ml). The aqueous phase is extracted twice with in each case 100 ml of ethyl acetate/cyclohexane (1:1). The combined organic phases are washed with water and saturated sodium chloride solution and dried over sodium sulfate. The solvent is removed under reduced pressure, giving an oil which crystallizes after addition of cyclohexane. The crystals are filtered off with suction and washed thoroughly with cyclohexane, giving a solid.

1. temperaturecooled to RT
2. temperatureheated at 100° C. for one hour
3. customThe cooled reaction mixture
4. extractionThe aqueous phase is extracted twice with in each case 100 ml of ethyl acetate/cyclohexane (1:1)
5. washThe combined organic phases are washed with water and saturated sodium chloride solution
6. dry with materialdried over sodium sulfate
7. customThe solvent is removed under reduced pressure
8. customgiving an oil which
9. customcrystallizes
10. additionafter addition of cyclohexane
11. filtrationThe crystals are filtered off with suction
12. washwashed thoroughly with cyclohexane
13. customgiving a solid

ORD record

ord-bf8102231d3348d2b0f9f8d86f7de5d0

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723347B2