Sodium Carbonate → 2,4'-Difluoro-3-hydroxy-[1,1'-biphenyl]-4-carbaldehyde

(4-Fluorophenyl)boronic acid (33.2 g), 2M aqueous sodium carbonate solution (237 mL), palladium (II) acetate (2.49 g) and dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (9.74 g) were added to a solution of 4-bromo-3-fluoro-2-hydroxybenzaldehyde (34.6 g) in DME (350 mL) at room temperature. The mixture was stirred at 100 C under argon atmosphere for 16 hours. The mixture was cooled to room temperature. Water (700 mL) was added to the reaction mixture. The mixture was concentrated in vacuo to remove DME. The precipitate was collected by filtration and washed with water. The aqueous filtrate was set aside for further purification. Then the solid was washed with ethyl acetate. The solid was added to a mixture of ethyl acetate and 1M hydrochloric acid. The mixture was stirred at room temperature for 1 hour and filtrated through celite. The filtrate was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (20.6 g).

1. concentrationThe mixture was concentrated in vacuo
2. customto remove DME
3. filtrationThe precipitate was collected by filtration
4. washwashed with water
5. customThe aqueous filtrate was set aside for further purification
6. washThen the solid was washed with ethyl acetate
7. additionThe solid was added to a mixture of ethyl acetate and 1M hydrochloric acid
8. stirringThe mixture was stirred at room temperature for 1 hour
9. filtrationfiltrated through celite
10. extractionThe filtrate was extracted with ethyl acetate
11. customThe organic layer was separated
12. washwashed with water and brine
13. dry with materialdried over anhydrous magnesium sulfate
14. concentrationconcentrated in vacuo

ORD 기록

ord-62a604b2aa7f40ffa8975bf7d363b4cc

출처 데이터셋

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09120777B2