Sulfuric Acid → 2-methyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indole

HRID 403630Notes

Reaction equation

HRID 403630 reaction equation
[C:1]1([NH:7]N)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:9][N:10]1[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]1.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+].[OH-].[Na+]>O1CCOCC1>[CH3:9][N:10]1[CH2:15][CH2:14][C:13]2[NH:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=3[C:12]=2[CH2:11]1

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 7516PhenylhydrazineHCID 14798Sodium HydroxideHCID 740491-Methyl-4-piperidoneHCID 516892Sodium Bicarbonate

Product 1

HCID 974242-methyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indoleYield 93%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

Phenyl hydrazine (1.0 g, 9.3 mmols) and 1-methyl-piperidin-4-one (1.1 g, 9.3 mmols) were dissolved in 1,4-dioxane (35 mL) and cooled to 0° C. Concentrated sulfuric acid (5 mL) was added dropwise to the reaction at 0° C. with stirring upon which a precipitate formed. The reaction was then heated to 60° C. for one hour after which the precipitate was fully dissolved. The reaction was stirred for an additional hour at 60° C. The reaction was then cooled to room temperature and the pH was adjusted to approximately 12 by the addition of saturated aqueous sodium bicarbonate solution followed by small portions of solid sodium hydroxide. The organic products were extracted with chloroform (3×20 mL) and the combined organic extracts were washed with brine (15 mL), dried (Na2SO4) and concentrated in vacuo. Purification by column chromatography (0-80% gradient of ethyl acetate in hexane) afforded the final product (1.6 g, 93% yield) as a beige solid. 1H NMR (400 MHz, DMSO): δ 10.80 (s, 1H), 7.30 (m, 2H), 6.98 (m, 2H), 3.53 (s, 2H), 2.79 (t, J=5.2 Hz, 2H), 2.71 (t, 2H, J=5.4 Hz), 2.43 (s, 3H). 13C NMR APT (100 MHz, CDCl3): δ 136.2 (up), 132.0 (up), 126.0 (up), 121.0 (down), 119.1 (down), 117.4 (down), 110.7 (down), 108.3 (up), 52.5 (up), 51.8 (up), 45.8 (down), 23.5 (up). ESI-HRMS (m/z): [M+H]+ calcd. for C12H14N2, 187.1230. found, 187.1228

Workup

  1. customformed
  2. temperatureThe reaction was then heated to 60° C. for one hour after which the precipitate
  3. dissolutionwas fully dissolved
  4. stirringThe reaction was stirred for an additional hour at 60° C
  5. temperatureThe reaction was then cooled to room temperature
  6. extractionThe organic products were extracted with chloroform (3×20 mL)
  7. washthe combined organic extracts were washed with brine (15 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography (0-80% gradient of ethyl acetate in hexane)

Sources & evidence

ORD record
ord-0c065a13c1a146d5988ff20cf8b2d04c
Source dataset
uspto-grants-2014_06
Patent number
US08748451B2

Reaction notes

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