Aluminium lithium hydride → 5-Bromo-1H-indole-3-ethanol

HRID 402306Notes

Reaction equation

HRID 402306 reaction equation
C[O:2][C:3](=O)[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([Br:14])[CH:12]=2)[NH:7][CH:6]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Br:14][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:4][CH2:3][OH:2]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 49782545methyl 2-(5-bromo-1H-indol-3-yl)acetate

Product 1

HCID 1229565-Bromo-1H-indole-3-ethanolYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The method of Bascop, S. I.; Laronze, J. Y.; Sapi, J. Synthesis of 2-aminopropyle-3-indole-acetic(propionic) acid derivatives. ARKIVOC 2003, 46-61, was followed. To a solution of ester 12 (4 mmol, 1 equiv) in anhydrous THF (50 mL) was added lithium aluminium hydride (LiAlH4; 16 mmol, 4 equiv) in portions with the temperature maintained at 0° C. The reaction mixture was brought to room temperature and stirred for 30 min. Excess LiAlH4 was destroyed by careful addition of a saturated aqueous solution of Na2SO4 with the temperature maintained at about 0° C. The mixture was filtered and the filtrate washed with THF. The combined filtrates were concentrated under reduced pressure, the residue was acidified to pH 6 with 10% HCl and extracted with CHCl3. The combined organic layer was dried (anhydrous Na2SO4), filtered, evaporated to dryness and purified using flash column chromatography by elution with EtOAc/hexane to give the alcohol 13. Yield: 83%; NMR (300 MHz, CDCl3): δ 2.97 (t, J=18 Hz, 2 H), 3.86-3.93 (m, 2 H), 4.09 (t, J=21 Hz, 1 H), 7.09 (d, J=3 Hz, 1 H), 7.22 (d, J=9 Hz, 1 H), 7.75 (s, 1 H), 8.10 (s, 1 H); MS (APCI): m/z 241.2 [M+H]+.

Workup

  1. customwas brought to room temperature
  2. customExcess LiAlH4 was destroyed by careful addition of a saturated aqueous solution of Na2SO4 with the temperature
  3. temperaturemaintained at about 0° C
  4. filtrationThe mixture was filtered
  5. washthe filtrate washed with THF
  6. concentrationThe combined filtrates were concentrated under reduced pressure
  7. extractionextracted with CHCl3
  8. dry with materialThe combined organic layer was dried (anhydrous Na2SO4)
  9. filtrationfiltered
  10. customevaporated to dryness
  11. custompurified
  12. washby elution with EtOAc/hexane

Sources & evidence

ORD record
ord-a6e4815368d44eada7e8ea89c9a02451
Source dataset
uspto-grants-2014_06
Patent number
US08742100B2

Reaction notes

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