Nitrogen → 5-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridine

HRID 44096

Reaction equation

HRID 44096 reaction equation
[Br:1][C:2]1[CH:3]=[C:4](I)[C:5]([OH:8])=[N:6][CH:7]=1.[C:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)#[CH:11].N#N.CCOCC>C(N(CC)CC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 3283Diethyl EtherHCID 5226271-Ethynyl-4-fluorobenzeneHCID 178517595HCID 178517595, compound

Product 1

HCID 592337145-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridineYield 65.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

5-bromo-3-iodopyridin-2-ol (6.7 g, 22 mmol) (Heterocycles. 57, 1, pp 55), 1-ethynyl-4-fluorobenzene (4.03 g, 33.5 mmol), copper(I) iodide (0.255 g, 1.34 mmol), trans-dichlorobis(triphenylphosphine)palladium (II) (0.784 g, 1.12 mmol) were combined and evacuated/backfilled with N2 (3×) then diluted with triethylamine (223 mL) and heated to 90° C. for 2 hours. The solvent was evaporated and the residue was dissolved in EtOAc. The organic phase was washed with water (50 mL), brine, dried over Na2SO4, filtered, and concentrated. Trituration with Et2O afforded the expected product 5-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridine (4.2 g, 14.4 mmol, 64% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.35-8.42 (2H, m), 8.03 (2H, dd, J=8.78, 5.27 Hz), 7.46 (1H, s), 7.39 (2H, t, J=8.91 Hz). LC-MS retention time: 2.36 min; m/z (MH+): 292, 294. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in EtOAc
  3. washThe organic phase was washed with water (50 mL), brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b2364259c3b245729ef733d93dafa49f
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Linked notes

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