Ammonium Chloride → 2-tert-Butyl-1H-indole

HRID 1403963Notes

Reaction equation

HRID 1403963 reaction equation
[C:1]1([CH3:14])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=O)[C:9]([CH3:12])([CH3:11])[CH3:10].[Li]CCCC.[NH4+].[Cl-]>C1COCC1>[C:9]([C:8]1[NH:7][C:2]2[C:1]([CH:14]=1)=[CH:6][CH:5]=[CH:4][CH:3]=2)([CH3:12])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 27340052,2,2'-TrimethylpropionanilideHCID 178418339Butyllithium

Product 1

HCID 5941662-tert-Butyl-1H-indoleYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
15 °C

Procedure

To a solution of N-o-tolylpivalamide (30.0 g, 159 mmol) in dry THF (100 mL) was added dropwise n-BuLi (2.5 M in hexane, 190 mL) at 15° C. After addition, the mixture was stirred overnight at 15° C. The mixture was cooled in an ice-water bath and treated with saturated NH4Cl. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuum. The residue was purified by column chromatography on silica gel to give 2-tert-butyl-1H-indole (24 g, 88%). 1H NMR (300 MHz, CDCl3) δ 7.99 (br. s, 1H), 7.54 (d, J=7.2 Hz, 1H), 7.05 (d, J=7.8 Hz, 1H), 7.06-7.13 (m, 2H), 6.26 (s, 1H), 1.39 (s, 9H).

Workup

  1. additionAfter addition
  2. temperatureThe mixture was cooled in an ice-water bath
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuum
  8. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-8445442b33a74241a11666bd2b355eb9
Source dataset
uspto-grants-2014_12
Patent number
US08912199B2

Reaction notes

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