N,N-Dibutyl-2-[3-(2,2-dimethylpropanoyl)-6-methoxy-1H-indazol-1-yl]acetamide → 2-(tert-Butyl)-6-methoxy-1H-indole

HRID 490790Notes

Reaction equation

HRID 490790 reaction equation
C(N(CCCC)C(=O)C[N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[C:10]([C:19](=O)[C:20]([CH3:23])([CH3:22])[CH3:21])=N1)CCC.[Li]CCCC>C1COCC1>[C:20]([C:19]1[NH:8][C:16]2[C:11]([CH:10]=1)=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)([CH3:23])([CH3:22])[CH3:21]

Participants

4

Reactant 2

HCID 10453694N,N-Dibutyl-2-[3-(2,2-dimethylpropanoyl)-6-methoxy-1H-indazol-1-yl]acetamideHCID 178418339Butyllithium

Product 1

HCID 576755122-(tert-Butyl)-6-methoxy-1H-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 17.20 g N-(5-methoxy-2-methylphenyl)-2,2-dimethylpropanamide prepared in Step A above in 300 mL anhydrous THF under nitrogen in a −3° C. bath was added 62.2 mL 2.5 M n-BuLi in hexanes. After stirring for 1 hour, the cooling bath was removed. After four days, it was quenched by addition of saturated ammonium chloride solution and concentrated under reduced pressure to remove solvents. The residue was diluted with 1 N HCl and extracted with ether. The combine ether extract was washed with 5% NaHCO3, and saturated brine, dried over anhydrous Na2SO4 and evaporated to give a crude product. It was purified by SGC with 10-25% EtOAc in hexanes to give title compound as yellowish solid followed by recovered starting material. 1H NMR (CDCl3, 500 MHz) δ 7.85 (br s, 1NH), 7.42 (d, J=8.7 Hz, 1H), 6.87 (d, J=2.3 Hz, 1H), 6.77 (dd, J=2.3 & 8.4 Hz, 1H), 6.19 (d, J=2.2 Hz, 1H), 3.86 (s, 3H), 1.40 (s, 9H). LC-MS: 3.68 min. (m/Z=204.1).

Workup

  1. customthe cooling bath was removed
  2. waitAfter four days
  3. customit was quenched by addition of saturated ammonium chloride solution
  4. concentrationconcentrated under reduced pressure
  5. customto remove solvents
  6. additionThe residue was diluted with 1 N HCl
  7. extractionextracted with ether
  8. extractionThe combine ether extract
  9. washwas washed with 5% NaHCO3, and saturated brine
  10. dry with materialdried over anhydrous Na2SO4
  11. customevaporated
  12. customto give a crude product
  13. customIt was purified by SGC with 10-25% EtOAc in hexanes

Sources & evidence

ORD record
ord-a9f768427e8640de898240c0820c1c96
Source dataset
uspto-grants-2009_05
Patent number
US07528163B2

Reaction notes

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