1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde → 1-(1H-pyrrolo[2,3-c]pyridin-2-yl)ethanol

HRID 1821865Notes

Reaction equation

HRID 1821865 reaction equation
[NH:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[CH:10]=[O:11].[CH3:12][Mg]Cl>C1COCC1>[NH:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[CH:10]([OH:11])[CH3:12]

Participants

4

Reactant 2

HCID 468564601H-pyrrolo[2,3-c]pyridine-2-carbaldehydeHCID 178418332HCID 178418332, compound

Product 1

HCID 578934541-(1H-pyrrolo[2,3-c]pyridin-2-yl)ethanolYield 75.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1H-pyrrolo[2,3-c]pyridine-2-carboxaldehyde (0.80 g, 5.47 mmol) in THF (27.4 mL) was slowly added methylmagnesium chloride (22% by weight in THF, 5.0 mL, 15.3 mmol) at 0° C. under a nitrogen atmosphere. The ice/water bath was removed, and the reaction mixture was stirred for 45 min. The reaction mixture was quenched with methanol and concentrated to dryness. The solid residue was treated with water (50 mL) and sonicated. The solids were filtered and collected, but they were shown to be undesired material. The water filtrate was concentrated to dryness, treated with 6 N HCl (2.55 mL) and concentrated to dryness again. The resulting orange solid was diluted with EtOAc and treated with saturated NaHCO3. The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were washed with saturated NaCl and dried over Na2SO4. The organic extract was filtered and concentrated to provide 1-(1H-pyrrolo[2,3-c]pyridin-2-yl)ethanol (0.67 g, 75%) as a tan solid: 1H NMR (300 MHz, CD3OD) δ1.59 (3H, d, J=6.6 Hz), 5.05 (1H, q, J=6.6 Hz), 6.41 (1H, s), 7.49-7.51 (1H, m), 8.00 (1H, d, J=5.6 Hz), 8.60 (1H, s); ESI MS m/z 163 [C9H10N2O+H]+; HPLC (Method A) 89.0% (AUC), tR=9.34 min.

Workup

  1. customat 0° C.
  2. customThe ice/water bath was removed
  3. customThe reaction mixture was quenched with methanol
  4. concentrationconcentrated to dryness
  5. additionThe solid residue was treated with water (50 mL)
  6. customsonicated
  7. filtrationThe solids were filtered
  8. customcollected
  9. concentrationThe water filtrate was concentrated to dryness
  10. additiontreated with 6 N HCl (2.55 mL)
  11. concentrationconcentrated to dryness again
  12. additionThe resulting orange solid was diluted with EtOAc
  13. additiontreated with saturated NaHCO3
  14. extractionThe aqueous layer was extracted with EtOAc (3×)
  15. washThe combined organic extracts were washed with saturated NaCl
  16. dry with materialdried over Na2SO4
  17. extractionThe organic extract
  18. filtrationwas filtered
  19. concentrationconcentrated

Sources & evidence

ORD record
ord-c5ae8ef838a44dde86d267136cfed454
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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