3-Methyl-2-butanone → 5-Methoxy-2,3,3-trimethyl-3H-indole

HRID 655096Notes

Reaction equation

HRID 655096 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]N)=[CH:5][CH:4]=1.[CH3:11][CH:12]([CH3:16])[C:13](=O)[CH3:14]>CC(O)=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]2[C:6](=[CH:5][CH:4]=1)[N:9]=[C:13]([CH3:14])[C:12]2([CH3:16])[CH3:11]

Participants

4

Reactant 2

HCID 112513-Methyl-2-butanoneHCID 77023(4-Methoxyphenyl)hydrazine

Product 1

HCID 110953925-Methoxy-2,3,3-trimethyl-3H-indoleYield 45.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4-methoxyphenyl)hydrazine (0.98 g, 7.1 mmol) and 3-methylbutan-2-one (1.53 g, 17.8 mmol) in 20 mL of HOAc was heated at 100° C. overnight. The mixture was concentrated and 1N NaOH was added until pH 9 to 10. The aqueous solution was extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over Na2SO4. After filtration and concentration, the residue was purified by flash column chromatography to give 610 mg of 5-methoxy-2,3,3-trimethyl-3H-indole (45%). 1H NMR (CDCl3) δppm: 7.43 (dd, 1H), 6.81 (m, 2H), 3.83 (s, 3H), 2.26 (s, 3H), 1.28 (s, 6H). LC-MS (M+H): 190.16

Workup

  1. concentrationThe mixture was concentrated
  2. addition1N NaOH was added until pH 9 to 10
  3. extractionThe aqueous solution was extracted with ethyl acetate (50 mL×3)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-b2fe6831fb734c919a3f468d16151cf9
Source dataset
uspto-grants-2011_12
Patent number
US08071388B2

Reaction notes

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