Dimethylformamide → 3-(1-cyano-1-methylethyl)-N-(3-hydroxy-4-methoxyphenyl)benzamide

To a solution (20 mL) of 3-(1-cyano-1-methylethyl)benzoic acid (4.92 g, 26.0 mmol) in oxalyl chloride was added N,N-dimethylformamide (0.1 mL), and the mixture was stirred at room temperature for 30 min. Excess reagents were evaporated under reduced pressure, and the obtained residue was dissolved in tetrahydrofuran (20 mL), and 5-amino-2-methoxyphenol (4.17 g, 30.0 mmol) and N-ethyl-N-isopropylpropane-2-amine (6.46 g, 50.0 mmol) were successively added dropwise under ice-cooling. The reaction mixture was stirred at room temperature for 18 hr, poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (5 mL)/tetrahydrofuran (5 mL), 8N aqueous sodium hydroxide solution (1 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=5:1), and triturated with diethyl ether to give the title compound (4.70 g, 58%) as a pale-yellow solid.

1. customExcess reagents were evaporated under reduced pressure
2. dissolutionthe obtained residue was dissolved in tetrahydrofuran (20 mL)
3. temperaturecooling
4. stirringThe reaction mixture was stirred at room temperature for 18 hr
5. extractionthe mixture was extracted with ethyl acetate
6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
7. customthe solvent was evaporated under reduced pressure
8. dissolutionThe residue was dissolved in methanol (5 mL)/tetrahydrofuran (5 mL), 8N aqueous sodium hydroxide solution (1 mL)
9. additionwas added under ice-
10. temperaturecooling
11. stirringthe mixture was stirred at room temperature for 18 hr
12. additionThe reaction mixture was poured into water
13. extractionthe mixture was extracted with ethyl acetate
14. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
15. customthe solvent was evaporated under reduced pressure
16. customThe residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=5:1)
17. customtriturated with diethyl ether

ORD 기록

ord-59b9d98a0ecb49cf94cc0daa18ef333d

출처 데이터셋

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08324395B2