Water → HCID 67308851, compound

To a solution of 4-hydroxynaphthalene-2-carboxylic acid ethyl ester (2.16 g) and pyridine (1.60 mL) in dichloromethane (100 mL) was added trifluoromethanesulfonic anhydride (2.5 mL) under ice-cooling, and the mixture was stirred at the same temperature for 10 minutes. To the reaction solution was added water (30 mL), and the resulting mixture was extracted with diethyl ether. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in N-methylpyrrolidone (33 mL). To the solution were added zinc cyanide (1.41 g) and tetrakis(triphenylphosphine)palladium (0.58 g), and the resulting mixture was stirred at 110° C. for 40 minutes. After the reaction mixture was cooled to room temperature, water (50 ml) and dichloromethane (50 mL) were added to the reaction solution. The insoluble material was removed by filtering through a Celite pad. The aqueous layer was separated, and the organic layer was filtered through an aminopropyl silica gel (eluent: dichloromethane). The organic layer was concentrated under reduced pressure. To the residue was added ethyl acetate (20 mL), and the mixture was washed with water (30 mL, 5 times). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate) to give 4-cyanonaphthalene-2-carboxylic acid ethyl ester (2.25 g). To a mixed solution of this compound (0.45 g) in tetrahydrofuran (10 mL), ethanol (5.0 mL) and water (5.0 mL) was added lithium hydroxide monohydrate (0.25 g), and the mixture was stirred for 1 hour. To the reaction solution was added water (20 mL), and the resulting mixture was washed with diethyl ether. To the aqueous layer was added 1 mol/L hydrochloric acid (3.3 mL), and the precipitated solid was collected by filtration. The obtained solid was dried under reduced pressure at 50° C. to give the title compound (0.37 g).

1. temperaturecooling
2. extractionthe resulting mixture was extracted with diethyl ether
3. washThe organic layer was washed with brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. dissolutionThe residue was dissolved in N-methylpyrrolidone (33 mL)
7. additionTo the solution were added zinc cyanide (1.41 g) and tetrakis(triphenylphosphine)palladium (0.58 g)
8. stirringthe resulting mixture was stirred at 110° C. for 40 minutes
9. additionwater (50 ml) and dichloromethane (50 mL) were added to the reaction solution
10. customThe insoluble material was removed
11. filtrationby filtering through a Celite pad
12. customThe aqueous layer was separated
13. filtrationthe organic layer was filtered through an aminopropyl silica gel (eluent: dichloromethane)
14. concentrationThe organic layer was concentrated under reduced pressure
15. additionTo the residue was added ethyl acetate (20 mL)
16. washthe mixture was washed with water (30 mL, 5 times)
17. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
18. concentrationconcentrated under reduced pressure
19. customThe obtained residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate)

ORD record

ord-130639bfecf84f4896accb9dceb4e403

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263622B2