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

HRID 1994198Notes

Reaction equation

HRID 1994198 reaction equation
C([Si](C)(C)[N:6]1[C:10]2=[N:11][CH:12]=[C:13]([Sn](CCCC)(CCCC)CCCC)[CH:14]=[C:9]2[CH2:8][CH2:7]1)(C)(C)C.[C:30]1([CH2:36]Br)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C1COCC1.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>[CH2:36]([C:13]1[CH:14]=[C:9]2[CH2:8][CH2:7][NH:6][C:10]2=[N:11][CH:12]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 2

HCID 7498Benzyl BromideHCID 587309311-(tert-Butyl-dimethyl-silanyl)-5-tributylstannanyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 587309565-benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridineYield 14.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of the crude stannane 17 (172 mg, 0.33 mmol) in THF (2.5 mL) was added PhCH2Br (0.03 mL, 0.27 mmol) and (Ph3P)2PdCl2 (5 mg, 0.007 mmol). The mixture was refluxed under N2 for 19 h, cooled, and partitioned between AcOEt-brine. The aqueous layer was extracted with AcOEt (2×). The combined organic solutions were dried (MgSO4), and concentrated in vacuum. The residual yellow oil was dissolved in MeOH (3 mL) and treated with a 10% solution of HCl in MeOH (2 mL). The mixture was stirred for 2.5 h, neutralized with saturated aqueous NaHCO3 solution and extracted with AcOEt (2×). The combined organic extracts were dried (MgSO4), concentrated, and purified by PTLC with CH2Cl2:MeOH=95:5 as eluent to afford the 5-benzyl derivative 18 (8 mg, 11% over 2 steps). 1H NMR (400 MHz; CDCl3) δ 2.99 (t, J=8.1 Hz, 2H), 3.60 (t, J=8.3 Hz, 2H), 3.79 (s, 2H), 7.06-7.31 (m, 7H), 7.69 (br s, NH).

Workup

  1. temperatureThe mixture was refluxed under N2 for 19 h
  2. temperaturecooled
  3. custompartitioned between AcOEt-brine
  4. extractionThe aqueous layer was extracted with AcOEt (2×)
  5. dry with materialThe combined organic solutions were dried (MgSO4)
  6. concentrationconcentrated in vacuum
  7. dissolutionThe residual yellow oil was dissolved in MeOH (3 mL)
  8. additiontreated with a 10% solution of HCl in MeOH (2 mL)
  9. extractionextracted with AcOEt (2×)
  10. dry with materialThe combined organic extracts were dried (MgSO4)
  11. concentrationconcentrated
  12. custompurified by PTLC with CH2Cl2

Sources & evidence

ORD record
ord-8aa7077c32774cef9d41dfc86a031c2f
Source dataset
uspto-grants-2010_01
Patent number
US07652137B2

Reaction notes

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