Hydrochloric Acid → HCID 10444194, compound

In a similar device as in Example 1 were charged 3.40 g (62.9 mmol) of sodium methoxide and 30 ml of dimethyl sulfoxide under argon atmosphere, then, while stirring at room temperature, 6.30 g (62.9 mmol) of methyl cyanoacetate with a purity of 99% was gradually added dropwise over 5 minutes. Moreover, 10 ml of cyclohexane was added to the mixture, and the temperature of the mixture was raised to 100 to 105° C., formed methanol was subjected to distillation (azeotropic distillation) with cyclohexane. This operation (distillation of methanol) was repeated twice, then, the mixture was cooled to room temperature, 5.10 g (41.9 mmol) of 2,4-difluoronitrobenzene with a purity of 98% was gradually added dropwise to the mixture over 10 minutes while maintaining the temperature to 30 to 40° C., and the resulting mixture was reacted by raising the temperature to 75° C. for one hour. After completion of the reaction, the mixture was cooled to room temperature, then, 100 ml of ethyl acetate was added to the mixture, and 5.25 ml (31.4 mmol) of 6 mol/l hydrochloric acid was gradually added dropwise to the mixture while stirring. Then, the organic layer was separated, and 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 5.48 g of methyl 2-(5-fluoro-2-nitrophenyl)-2-cyanoacetate (isolation yield: 71%) as a yellowish oily product with a purity of 97% (areal percentage by high performance liquid chromatography).

1. temperaturethe temperature of the mixture was raised to 100 to 105° C.
2. distillationwas subjected to distillation (azeotropic distillation) with cyclohexane
3. distillationThis operation (distillation of methanol)
4. temperaturethe mixture was cooled to room temperature
5. temperaturewhile maintaining the temperature to 30 to 40° C.
6. customthe resulting mixture was reacted
7. temperatureby raising the temperature to 75° C. for one hour
8. customAfter completion of the reaction
9. temperaturethe mixture was cooled to room temperature
10. additionwas gradually added dropwise to the mixture
11. stirringwhile stirring
12. customThen, the organic layer was separated
13. washwashed 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-b479a729c4fc41ad94a0afb4fd6cb39c

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07342040B2