Stannane, tributyl(1-ethoxyethenyl)- → HCID 86689828, compound

HRID 2409017Notes

Reaction equation

HRID 2409017 reaction equation
C([Sn](CCCC)(CCCC)[C:6]([O:8]CC)=[CH2:7])CCC.Cl[C:20]1[N:25]=[C:24]2[CH:26]=[CH:27][N:28](C(OC(C)(C)C)=O)[C:23]2=[CH:22][CH:21]=1>CN(C=O)C.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:28]1[C:23]2[C:24](=[N:25][C:20]([C:6](=[O:8])[CH3:7])=[CH:21][CH:22]=2)[CH:26]=[CH:27]1

Participants

6

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 86689827HCID 86689827, compound

Product 1

HCID 86689828HCID 86689828, compoundYield 64.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A high-pressure tube was charged with tributyl(1-ethoxyvinyl)stannane (7.75 g, 21.45 mmol) and tert-butyl 5-chloropyrrolo[3,2-b]pyridine-1-carboxylate (4.17 g, 16.50 mmol) in degassed DMF (64.0 mL) and Pd(PPh3)4 (1.9 g, 1.65 mmol) was added in one batch. The tube was closely tightly and the reaction mixture was stirred at 100° C. under N2 for 2 d. The reaction mixture was cooled, diluted with EtOAc (350 mL), and filtered through a pad of Celite® to remove solid Pd. The filtrate was washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was dissolved in anhydrous THF (80.2 mL), and 2N HCl (41 mL) was added. The reaction mixture was stirred at RT under N2 for 16 h, poured into 10% aq. NaOH solution (100 mL) and then extracted with EtOAc (3×150 mL). The combined organic phases were washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by SiO2chromatography eluting with EtOAc/heptane to afford 1.69 g (64.1%) of 1-(1H-pyrrolo[3,2-b]-pyridin-5-yl)ethanone as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H), 7.99 (d, J=8.5 Hz, 1H), 7.74 (d, J=8.5 Hz, 1H), 7.54 (t, J=3.0 Hz, 1H), 6.86 (s, 1H), 2.80 (s, 3H); MS (ESI) m/z: 161.3 [M+1]+.

Workup

  1. additionwas added in one batch
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered through a pad of Celite®
  4. customto remove solid Pd
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe crude product was dissolved in anhydrous THF (80.2 mL)
  10. addition2N HCl (41 mL) was added
  11. stirringThe reaction mixture was stirred at RT under N2 for 16 h
  12. additionpoured into 10% aq. NaOH solution (100 mL)
  13. extractionextracted with EtOAc (3×150 mL)
  14. washThe combined organic phases were washed with water and brine
  15. dry with materialdried (Na2SO4)
  16. filtrationfiltered
  17. concentrationconcentrated under reduced pressure
  18. customThe crude product was purified by SiO2chromatography
  19. washeluting with EtOAc/heptane

Sources & evidence

ORD record
ord-fe445288fa9149bebd8143a2f5a5c93d
Source dataset
uspto-grants-2014_08
Patent number
US08815877B2

Reaction notes

Loading…