反应详情

温度

100 °C

Methyl 5-bromo-2-methoxybenzoate (29.3 g) obtained in step A of Example 1-1-1, and 33.1 g of zinc cyanide were dissolved in 650 mL of N,N-dimethylformamide. N,N-Dimethylformamide was degassed under reduced pressure, and then the interior of the reactor was purged with nitrogen. After 9.8 g of tetrakistriphenylphosphine palladium was added, N,N-dimethylformamide was deaerated again under reduced pressure, and then the interior of the reactor was purged with argon. This solution was stirred for 2 hours at 100° C., whereafter the solvent was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate. The insolubles were removed by filtration, and washed with ethyl acetate. The filtrate and the washings were combined, water was added, and then the organic layer was separated. The aqueous layer was extracted twice with ethyl acetate. After the respective organic layers were combined, the combined organic layer was washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The anhydrous sodium sulfate was separated by filtration, and then washed with ethyl acetate. The filtrate and the washings were combined, and ethyl acetate was distilled off under reduced pressure. The resulting residue was washed with diethyl ether. The resulting solid was dried under reduced pressure to obtain 13.5 g (42%) of methyl 5-cyano-2-methoxybenzoate. The mother liquor and the washings were combined, and concentrated, whereafter the residue was recrystallized from t-butyl methyl ether. The resulting crystals were separated by filtration, then washed with a 1:1 solvent mixture of n-hexane and diethyl ether, and then dried under reduced pressure to obtain 4.6 g (14%) of methyl 5-cyano-2-methoxybenzoate.

1. customN,N-Dimethylformamide was degassed under reduced pressure
2. customthe interior of the reactor was purged with nitrogen
3. additionAfter 9.8 g of tetrakistriphenylphosphine palladium was added
4. customthe interior of the reactor was purged with argon
5. distillationwas distilled off under reduced pressure
6. dissolutionthe residue was dissolved in ethyl acetate
7. customThe insolubles were removed by filtration
8. washwashed with ethyl acetate
9. additionwater was added
10. customthe organic layer was separated
11. extractionThe aqueous layer was extracted twice with ethyl acetate
12. washthe combined organic layer was washed with a saturated aqueous solution of sodium chloride
13. dry with materialdried over anhydrous sodium sulfate
14. customThe anhydrous sodium sulfate was separated by filtration
15. washwashed with ethyl acetate
16. distillationethyl acetate was distilled off under reduced pressure
17. washThe resulting residue was washed with diethyl ether
18. customThe resulting solid was dried under reduced pressure