Acetyl chloride → 1-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)ethan-1-one

HRID 901497Notes

Reaction equation

HRID 901497 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[Br:5][C:6]1[CH:7]=[C:8]2[CH:14]=[CH:13][NH:12][C:9]2=[N:10][CH:11]=1.[C:15](Cl)(=[O:17])[CH3:16]>C(Cl)Cl>[Br:5][C:6]1[CH:7]=[C:8]2[C:14]([C:15](=[O:17])[CH3:16])=[CH:13][NH:12][C:9]2=[N:10][CH:11]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 596999141-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)ethan-1-oneYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring solution of aluminum chloride (6.77 g, 50.75 mmol) suspended in anhydrous CH2Cl2 (100 mL) under N2 was added 5-bromo-1H-pyrrolo[2,3-b]pyridine (2.00 g, 10.15 mmol). The reaction solution was stirred for 1 hour at ambient temperature whereupon acetyl chloride (3.61 mL, 50.75 mmol) was added dropwise and the resulting solution was stirred for 5 more hours. The reaction was cooled to 0° C. in an ice bath and quenched carefully by addition of MeOH until the solution became clear. The reaction was concentrated under vacuum. H2O was added and 1 N NaOH was added dropwise until the pH=4. The product was extracted into ethyl acetate and the organic layer was washed with a saturated solution of sodium potassium tartrate to remove any remaining aluminum salts. The organic layer was dried over Na2SO4 and concentrated under vacuum. The material was redissolved in ethyl acetate and filtered through a bed of silica gel. The filtrate was concentrated to afford the title compound as an orange solid (2.25 g, 93% yield). 1H NMR (500 MHz, d6-DMSO) δ 12.70 (br s, 1H), 8.56 (d, J=2.5 Hz, 1H), 8.55 (s, 1H), 8.40 (d, J=2.5 Hz, 1H), 2.46 (s, 3H). MS: m/z 238.9/240.9 (M+H+).

Workup

  1. additionwas added dropwise
  2. customquenched carefully by addition of MeOH until the solution
  3. concentrationThe reaction was concentrated under vacuum
  4. additionH2O was added
  5. addition1 N NaOH was added dropwise until the pH=4
  6. extractionThe product was extracted into ethyl acetate
  7. washthe organic layer was washed with a saturated solution of sodium potassium tartrate
  8. customto remove any remaining aluminum salts
  9. dry with materialThe organic layer was dried over Na2SO4
  10. concentrationconcentrated under vacuum
  11. dissolutionThe material was redissolved in ethyl acetate
  12. filtrationfiltered through a bed of silica gel
  13. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-4819d1dcf97b4a408891a2c049d49c54
Source dataset
uspto-grants-2008_04
Patent number
US07361764B2

Reaction notes

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