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

To a solution of 3-(1-cyano-1-methylethyl)benzoic acid (4.92 g, 26.0 mmol) produced in Example C6(ii) in oxalyl chloride (20 mL) was added N,N-dimethylformamide (0.1 mL), and the mixture was stirred at room temperature for 30 min. Excessive reagent was evaporated under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (20 mL), and 5-amino-2-methoxyphenol (4.17 g, 30.0 mmol) and N-ethyl-N-(1-methylethyl)propan-2-amine (6.46 g, 50.0 mmol) were sequentially added dropwise under ice-cooling. The reaction solution was stirred at room temperature for 18 hr, and poured into water. 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 solution 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 (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. customExcessive reagent was evaporated under reduced pressure
2. dissolutionthe obtained residue was dissolved in tetrahydrofuran (20 mL)
3. temperaturecooling
4. stirringThe reaction solution 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 solution 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 (hexane/ethyl acetate=5:1)
17. customtriturated with diethyl ether

ORDレコード

ord-fa4125b37c05461c8e86ba948620e06a

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08344135B2