Benzyl Bromide → 1-benzyl-2-bromo-5-chloro-1H-pyrrolo[3,2-b]pyridine

HRID 628304Notes

Reaction equation

HRID 628304 reaction equation
[OH-].[Na+].FC(F)(F)C(O)=O.[Br:10][C:11]1[N:19](S(C2C=CC=CC=2)(=O)=O)[C:18]2[C:13](=[N:14][C:15]([Cl:29])=[CH:16][CH:17]=2)[CH:12]=1.C([O-])([O-])=O.[K+].[K+].[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1.CO.CN(C=O)C.O>[CH2:36]([N:19]1[C:18]2[C:13](=[N:14][C:15]([Cl:29])=[CH:16][CH:17]=2)[CH:12]=[C:11]1[Br:10])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

9

Reactant 4

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 1181597152-bromo-5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine trifluoroacetate salt

Product 1

HCID 1181595111-benzyl-2-bromo-5-chloro-1H-pyrrolo[3,2-b]pyridine

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

1.0 M NaOH in water (5 mL, 5 mmol) was added to a solution of 2-bromo-5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine trifluoroacetate (0.268 g, 0.552 mmol, from Step 1) in THF (5 mL) and methanol (5 mL) and the reaction was stirred for 1 hour. Water was added and THF and MeOH were removed in vacuo. The product was extracted with EtOAc. The extracts were dried over sodium sulfate, filtered and concentrated. A solution of this residue in DMF (3 mL) was treated with K2CO3 (0.23 g, 1.6 mmol) and benzyl bromide (0.0656 mL, 0.552 mmol, Aldrich). After stirring overnight, the reaction was partitioned between water and ethyl acetate and extracted a total of three times. The combined extracts were dried over sodium sulfate, filtered and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-30% EtOAc in hexanes to afford product as a white crystalline solid. Yield: (177 mg, 99%).

Workup

  1. customTHF and MeOH were removed in vacuo
  2. extractionThe product was extracted with EtOAc
  3. dry with materialThe extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringAfter stirring overnight
  7. customthe reaction was partitioned between water and ethyl acetate
  8. extractionextracted a total of three times
  9. dry with materialThe combined extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe product was purified by flash chromatography
  13. washeluting with a gradient from 0-30% EtOAc in hexanes
  14. customto afford product as a white crystalline solid

Sources & evidence

ORD record
ord-6e6788464e474adda697d21d34389230
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

Loading…