Potassium Carbonate → 2',5-Difluoro-5'-methoxy-[1,1'-biphenyl]-3-carbaldehyde

HRID 1504496Notes

Reaction equation

HRID 1504496 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[F:10].[F:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[C:16]([CH:18]=[O:19])[CH:17]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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:3]1[CH:4]=[CH:5][C:6]([O:8][CH3:9])=[CH:7][C:2]=1[C:14]1[CH:13]=[C:12]([F:11])[CH:17]=[C:16]([CH:18]=[O:19])[CH:15]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 177508692-Bromo-1-fluoro-4-methoxybenzeneHCID 222791933-Fluoro-5-formylphenylboronic acid

Product 1

HCID 1177371732',5-Difluoro-5'-methoxy-[1,1'-biphenyl]-3-carbaldehydeYield 28.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

To a RBF was added 2-bromo-1-fluoro-4-methoxybenzene (1.850 mL, 9.02 mmol, Oakwood), 3-fluoro-5-formylphenylboronic acid (1667 mg, 9.93 mmol, Combi-blocks), tetrakis(triphenylphosphine)palladium (521 mg, 0.451 mmol) and potassium carbonate (3741 mg, 27.1 mmol). A condenser and septum was attached and 1,4-dioxane (24.100 mL) and water (6.03 mL) were added. The mixture was heated at 90° C. for 2 h, at which time the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (2×50 mL). The organic extract was washed with brine (20 mL) and dried over MgSO4. The solution was filtered and concentrated. The residue was absorbed onto a plug of silica gel and purified by chromatography through a 50 g silica column, eluting with a gradient of 0% to 30% EtOAc in Heptane, to provide 2′,5-difluoro-5′-methoxy-[1,1′-biphenyl]-3-carbaldehyde (640 mg, 2.58 mmol, 28.6% yield) as white solid. 1H NMR (400 MHz, DMSO-d6) δ 10.01-10.14 (m, 1H), 8.01 (q, J=1.56 Hz, 1H), 7.82 (tdd, J=1.41, 2.59, 9.76 Hz, 1H), 7.67-7.78 (m, 1H), 7.32 (dd, J=9.65, 10.42 Hz, 1H), 7.18 (dd, J=3.23, 6.46 Hz, 1H), 7.05 (td, J=3.57, 9.00 Hz, 1H) 3.83 (s, 3H).

Workup

  1. customA condenser and septum was attached
  2. extractionextracted with EtOAc (2×50 mL)
  3. extractionThe organic extract
  4. washwas washed with brine (20 mL)
  5. dry with materialdried over MgSO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated
  8. customThe residue was absorbed onto a plug of silica gel
  9. custompurified by chromatography through a 50 g silica column
  10. washeluting with a gradient of 0% to 30% EtOAc in Heptane

Sources & evidence

ORD record
ord-240aaa682c2a442b8bdecfbead1ffff4
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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