Ethyl Acetate → 5-Fluoro-4'-(trifluoromethyl)biphenyl-2-carbaldehyde

HRID 524631Notes

Reaction equation

Br[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[F:11][C:12]([F:23])([F:22])[C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C([O-])(=O)C.[K+].CCOC(C)=O>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:10][C:8]1[CH:9]=[C:2]([C:16]2[CH:17]=[CH:18][C:13]([C:12]([F:23])([F:22])[F:11])=[CH:14][CH:15]=2)[C:3]([CH:4]=[O:5])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-bromo-4-fluorobenzaldehyde (2 g, 9.85 mmol), (4-(trifluoromethyl)phenyl)boronic acid (2.25 g, 11.82 mmol), potassium acetate (2.42 g, 24.63 mmol) and Pd(PPh3)4 (1.14 g, 0.98 mmol) in DMF (40 mL) and water (13 mL) was stirred at 100° C. for 3 hours under N2, then cooled to 25° C. To the mixture was added EtOAc (250 mL). The organic layer was washed with brine (200 mL×3), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=70/1) to give the title compound as colorless oil (2.11 g, 79%). The compound was characterized by the following spectroscopic data:

Workup

temperaturecooled to 25° C
washThe organic layer was washed with brine (200 mL×3)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo
customThe residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=70/1)

Sources & evidence

ORD record: ord-6c3ddd9517044f1eaa787ba97da392b2
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340538B2

Reaction notes

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