3-Fluorophenylboronic acid → 2-(3-Fluorophenyl)-4-methoxypyridine

HRID 1504369Notes

Reaction equation

HRID 1504369 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[F:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][CH:16]=1>CCOC(C)=O>[F:10][C:11]1[CH:16]=[C:15]([C:2]2[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=2)[CH:14]=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 27339863-Fluorophenylboronic acidHCID 47384842-Bromo-4-methoxypyridine

Product 1

HCID 463129782-(3-Fluorophenyl)-4-methoxypyridineYield 144%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A 100-mL recovery flask containing 2-bromo-4-methoxypyridine (1.446 g, 7.69 mmol, purchased from Combi-Blocks, Inc.), 3-fluorophenylboronic acid (2.152 g, 15.38 mmol, purchased from Oakwood Products, Inc.), and 1,1′-bis(diphenylphosphino)ferrocene palladium(11)dichloride dichloromethane adduct (0.314 g, 0.385 mmol) was flushed with N2 and subsequently charged with dioxane (29 mL) and 1.9 M Na2CO3 in H2O (10 mL). The black-red mixture was stirred at 85° C. overnight. The next morning, after cooling to rt, the dark red mixture was diluted with H2O and extracted thrice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to a black oil. Column chromatography (50 g Snap Ultra column, 10-100% EtOAc/hept) afforded 2-(3-fluorophenyl)-4-methoxypyridine (2.25 g, >99% yield) as a viscous yellow oil. m/z (ESI) 204.2 (M+H)+.

Workup

  1. customwas flushed with N2
  2. additionsubsequently charged with dioxane (29 mL) and 1.9 M Na2CO3 in H2O (10 mL)
  3. temperatureThe next morning, after cooling to rt
  4. additionthe dark red mixture was diluted with H2O
  5. extractionextracted thrice with EtOAc
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a black oil

Sources & evidence

ORD record
ord-f54a1dc1cffc4b1e8c356e8d164ef062
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

Loading…