Dimethyl Sulfoxide → 2',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)biphenyl-3-carbaldehyde

Temperature

80 °C

2-Bromo-1,3-dimethyl-5-[3-(methylsulfonyl)propoxy]benzene (250.0 g), 3-formylphenylboronic acid (122.5 g), tripotassium phosphate (330.4 g), 10% palladium carbon 50% water-containing product (12.5 g) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (5.5 g) were added to dimethyl sulfoxide (2500 mL) and water (1250 mL). After deaeration and nitrogen substitution, the mixture was heated, and stirred at 80° C. for 3 hr. The reaction mixture was left standing, and the oil component in the lower layer was removed. The mixture was cooled, ethyl acetate (875 mL) was added, and the mixture was stirred. The insoluble material was removed by filtration, and washed with ethyl acetate (625 mL). To the filtrate was added 10% brine (1500 mL), the mixture was stirred, and the organic layer was separated. The aqueous layer was extracted again with ethyl acetate (1500 mL). The organic layers were combined, and washed twice with 10% brine (1500 mL). The organic layer was concentrated to 750 mL, ethyl acetate (1500 mL) was added, and an operation to concentrate the mixture to 750 mL again was performed twice. To the concentrate were added ethyl acetate (1250 mL) and activated carbon (25 g), and the mixture was stirred at room temperature for 30 min. The insoluble material was removed by filtration, and washed with ethyl acetate (750 mL). The filtrate was concentrated to 750 mL under reduced pressure, and stirred at room temperature overnight. Normal heptane (3750 mL) was added dropwise, and the mixture was stirred at room temperature for 2 hr. The precipitated solid was collected by filtration, and the solid was washed with a mixture (750 mL) of ethyl acetate.normal heptane (1:5), and dried under reduced pressure to give 2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-carbaldehyde (235.0 g).

1. temperatureAfter deaeration and nitrogen substitution, the mixture was heated
2. waitThe reaction mixture was left
3. customthe oil component in the lower layer was removed
4. temperatureThe mixture was cooled
5. additionethyl acetate (875 mL) was added
6. stirringthe mixture was stirred
7. customThe insoluble material was removed by filtration
8. washwashed with ethyl acetate (625 mL)
9. additionTo the filtrate was added 10% brine (1500 mL)
10. stirringthe mixture was stirred
11. customthe organic layer was separated
12. extractionThe aqueous layer was extracted again with ethyl acetate (1500 mL)
13. washwashed twice with 10% brine (1500 mL)
14. concentrationThe organic layer was concentrated to 750 mL, ethyl acetate (1500 mL)
15. additionwas added
16. concentrationan operation to concentrate the mixture to 750 mL
17. additionTo the concentrate were added ethyl acetate (1250 mL) and activated carbon (25 g)
18. stirringthe mixture was stirred at room temperature for 30 min
19. customThe insoluble material was removed by filtration
20. washwashed with ethyl acetate (750 mL)
21. concentrationThe filtrate was concentrated to 750 mL under reduced pressure
22. stirringstirred at room temperature overnight
23. additionNormal heptane (3750 mL) was added dropwise
24. stirringthe mixture was stirred at room temperature for 2 hr
25. filtrationThe precipitated solid was collected by filtration
26. washthe solid was washed with a mixture (750 mL) of ethyl acetate
27. dry with materialnormal heptane (1:5), and dried under reduced pressure

ORD record

ord-afe408529f9c40389adffefc10784194

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952185B2