4-(Trifluoromethoxy)phenylhydrazine hydrochloride → 2-methyl-8-trifluoromethoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401409Notes

Reaction equation

HRID 1401409 reaction equation
Cl.[F:2][C:3]([F:14])([F:13])[O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11]N)=[CH:7][CH:6]=1.Cl.[CH3:16][N:17]1[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1>S(=O)(=O)(O)O.O1CCOCC1>[CH3:16][N:17]1[CH2:22][CH2:21][C:20]2[NH:11][C:8]3[CH:7]=[CH:6][C:5]([O:4][C:3]([F:14])([F:13])[F:2])=[CH:10][C:9]=3[C:19]=2[CH2:18]1

Participants

5

Reactant 2

HCID 27773284-(Trifluoromethoxy)phenylhydrazine hydrochlorideHCID 122100571-Methylpiperidin-4-one hydrochloride

Product 1

HCID 594549332-methyl-8-trifluoromethoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

(4-(Trifluoromethoxy)phenyl)hydrazine hydrochloride (1 equiv.) is taken in 7% sulfuric acid in 1,4-dioxane. 1-Methylpiperidin-4-one hydrochloride (0.76-1.4 equiv.) is added and the mixture is stirred at 80° C. for 6 h. The reaction is monitored by TLC and LCMS. After completion of the reaction, the reaction mixture is concentrated, then slowly quenched with aq. NaHCO3 solution and extracted with EtOAc. The organic layer is dried over anhydrous sodium sulfate, evaporated to dryness and purified by column chromatography to afford 2-methyl-8-(trifluoromethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole.

Workup

  1. customAfter completion of the reaction
  2. concentrationthe reaction mixture is concentrated
  3. customslowly quenched with aq. NaHCO3 solution
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  6. customevaporated to dryness
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-8d8feb9af5554639be72699f145cbe8f
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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