Hydrochloric Acid → HCID 10038811, compound

In a flask made of glass equipped with a stirrer, a thermometer, a distillation device and a dropping funnel and having an inner volume of 200 ml were charged 3.40 g (62.9 mmol) of sodium methoxide and 30 ml dimethyl sulfoxide under argon atmosphere, and then, while stirring at room temperature, 8.48 g (62.9 mmol) of dimethyl malonate with a purity of 98% was gradually added dropwise over 5 minutes. Moreover, 10 ml of cyclohexane was added to the mixture, and after raising the temperature to 100 to 105° C., the formed methanol was subjected to azeotropic distillation (removed by distillation) with cyclohexane. After this operation (removal of methanol by distillation) was repeated twice, the reaction mixture was cooled to 70° C., and 5.10 g (31.4 mmol) of 2,4-difluoro-nitrobenzene with a purity of 98% was gradually added dropwise over 10 minutes, and the resulting mixture was reacted at 70 to 80° C. for one hour. After completion of the reaction, the mixture was cooled to room temperature, 100 ml of toluene was added to the mixture and 5.25 ml (31.4 mmol) of 6 mol/l hydrochloric acid was gradually added dropwise while stirring. Then, the organic layer was separated, and the resulting mixture was washed successively with 50 ml of water and 50 ml of a saturated saline solution in this order, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography (filler: Daisogel 1002W, eluent: hexane:ethyl acetate=9:1 (volume ratio)) to obtain 5.60 g of dimethyl 2-(5-fluoro-2-nitrophenyl)malonate (isolation yield: 64%) as white crystals with a purity of 98% (areal percentage by high performance liquid chromatography)

1. customIn a flask made of glass
2. customequipped with a stirrer
3. temperatureafter raising the temperature to 100 to 105° C.
4. distillationthe formed methanol was subjected to azeotropic distillation (removed by distillation) with cyclohexane
5. customAfter this operation (removal of methanol by distillation)
6. temperaturethe reaction mixture was cooled to 70° C.
7. customthe resulting mixture was reacted at 70 to 80° C. for one hour
8. customAfter completion of the reaction
9. temperaturethe mixture was cooled to room temperature
10. additionwas gradually added dropwise
11. stirringwhile stirring
12. customThen, the organic layer was separated
13. washthe resulting mixture was washed successively with 50 ml of water and 50 ml of a saturated saline solution in this order
14. dry with materialdried over anhydrous magnesium sulfate
15. filtrationAfter filtration
16. concentrationthe filtrate was concentrated under reduced pressure
17. concentrationthe resulting concentrate
18. customwas purified by silica gel column chromatography (filler: Daisogel 1002W, eluent: hexane:ethyl acetate=9:1 (volume ratio))

ORD record

ord-1a6861f04cd24698b3e32b36238d77f1

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06900335B2