Sodium Hydroxide → 3-bromo-1-cyclopropyl-6-fluoro-1H-pyrrolo[2,3-b]pyridine

HRID 1622881Notes

Reaction equation

HRID 1622881 reaction equation
[CH:1]1([N:4]2[C:8]3=[N:9][C:10]([F:13])=[CH:11][CH:12]=[C:7]3[CH:6]=[CH:5]2)[CH2:3][CH2:2]1.[OH-].[Na+].[Br:16]N1C(=O)CCC1=O>CN(C=O)C>[Br:16][C:6]1[C:7]2[C:8](=[N:9][C:10]([F:13])=[CH:11][CH:12]=2)[N:4]([CH:1]2[CH2:3][CH2:2]2)[CH:5]=1

Participants

5

Reactant 3

HCID 14798Sodium Hydroxide3×HCID 67184N-bromobutanimide3×HCID 678162521-cyclopropyl-6-fluoro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 678163113-bromo-1-cyclopropyl-6-fluoro-1H-pyrrolo[2,3-b]pyridineYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-cyclopropyl-6-fluoro-1H-pyrrolo[2,3-b]pyridine (2.03 g, 11.52 mmol) in DMF (38 mL) is added sodium hydroxide (0.506 g, 12.67 mmol), followed by N-bromosuccinimide (2.26 g, 12.67 mmol) portionwise over 5 minutes, resulting in an exothermic reaction (28° C.). The mixture is stirred at room temperature for 15 min., and further sodium hydroxide (46.1 mg, 1.15 mmol) and N-bromosuccinimide (0.205 g, 1.15 mmol) are added. Stirring is continued at room temperature for 30 min. Further sodium hydroxide (46.1 mg, 1.15 mmol) and N-bromosuccinimide (0.205 g, 1.15 mmol) are added. The reaction mixture is stirred at room temperature for 16 h and then poured onto brine (ca. 500 mL) and extracted with CHCl3 (ca. 2×300 mL). The organic layers are combined and dried over magnesium sulphate, filtered, and concentrated in vacuo to give a brown oil, which is purified by column chromatography on silica, eluting with 0 to 100% DCM in isohexane, to give the title compound as a white powder (2.32 g, 9.10 mmol). MS (m/z): 255/257 (M+1).

Workup

  1. customresulting in an exothermic reaction (28° C.)
  2. stirringStirring
  3. waitis continued at room temperature for 30 min
  4. stirringThe reaction mixture is stirred at room temperature for 16 h
  5. additionpoured onto brine (ca. 500 mL)
  6. extractionextracted with CHCl3 (ca. 2×300 mL)
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a brown oil, which
  11. customis purified by column chromatography on silica
  12. washeluting with 0 to 100% DCM in isohexane

Sources & evidence

ORD record
ord-0eab9904b4dc4c5cb91684beef4f8e0b
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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