Dimethylformamide → 3-(3-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoic acid

HRID 44055Notes

Reaction equation

HRID 44055 reaction equation
C1C(=O)N([Br:8])C(=O)C1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[O:33][C:19]3=[N:20][CH:21]=[C:22]([C:24]4[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=4)[C:27]([OH:29])=[O:28])[CH:23]=[C:18]3[CH:17]=2)=[CH:12][CH:11]=1.CN(C=O)C>C1COCC1>[Br:8][C:17]1[C:18]2[C:19](=[N:20][CH:21]=[C:22]([C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27]([OH:29])=[O:28])[CH:23]=2)[O:33][C:16]=1[C:13]1[CH:12]=[CH:11][C:10]([F:9])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 67184N-bromobutanimide2×HCID 592337413-(2-(4-Fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoic acid

Product 1

HCID 592336883-(3-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoic acidYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

NBS (125 mg, 0.702 mmol) was added to a stirred suspension of 3-(2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoic acid (215 mg, 0.645 mmol) in THF (5 mL)/DMF (1 mL). The solids dissolved and the reaction was stirred at room temperature for 30 min, then quenched with 10% Na2S2O3, and acidified with 1N HCl. The solvent was evaporated and the material was diluted with water, filtered and dried to afford a mixture of starting material and product. The material was resubjected to the reaction conditions (80 mg of NBS in 3 mL THF/0.5 mL DMF). After 3 h, the reaction was quenched by the addition of 10% Na2S2O3, and the solution was acidified with 0.1N HCl. The volatiles were removed and the resulting off-white precipitate was collected by filtration, rinsed with water and Et2O, and air-dried to afford the expected product 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoic acid (140 mg, 53% yield) as an off-white powder consistent by LCMS and NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (1H, d, J=2.26 Hz), 8.27-8.33 (2H, m), 8.19-8.26 (2H, m), 8.05-8.12 (1H, m), 8.03 (1H, d, J=7.78 Hz), 7.68 (1H, t, J=7.78 Hz), 7.45-7.55 (2H, m). LC-MS retention time: 1.20 min; m/z (MH+): 412, 414. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 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 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. dissolutionThe solids dissolved
  2. customquenched with 10% Na2S2O3
  3. customThe solvent was evaporated
  4. additionthe material was diluted with water
  5. filtrationfiltered
  6. customdried
  7. customto afford
  8. additiona mixture of starting material and product
  9. waitAfter 3 h
  10. customthe reaction was quenched by the addition of 10% Na2S2O3
  11. customThe volatiles were removed
  12. filtrationthe resulting off-white precipitate was collected by filtration
  13. washrinsed with water and Et2O
  14. customair-dried

Sources & evidence

ORD record
ord-e98b5f2b0ed8490293820397b1754928
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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