Water → 2-(4-Fluorophenyl)-1-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)propan-2-ol

HRID 710897Notes

Reaction equation

HRID 710897 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2([CH3:28])[CH2:27][O:26]2)=[CH:21][CH:20]=1.O>C1COCC1.CN(C=O)C.C(OCC)(=O)C>[F:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]([OH:26])([CH3:27])[CH2:28][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]2=3)=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 178694862-(4-Fluorophenyl)-2-methyloxirane

Product 1

HCID 578761042-(4-Fluorophenyl)-1-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)propan-2-ol

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of compound 2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole (2.6 g, 13.1 mmol, 1 equiv.) and NaH (55%, 750 mg, 17.2 mmol, 1.3 equiv.) in 60 ml of THF was heated to 120 deg C. for 1 h. It was then cooled to RT and compound 2-(4-fluorophenyl)-2-methyloxirane (4 g, 26 mmol, 2 equiv.) in 25 ml of DMF was added dropwise for 5 mins at RT followed by heating at 120 deg C. for 2 h. It was cooled to RT and 10 ml of water was added followed by dilution with 800 ml of ethyl acetate, which was first washed with water (150 ml×3) and then brine, dried over sodium sulphate and concentrated under vacuum. Column purified over 230-400 Silica gel (flash) using 15% methanol in ethyl acetate as eluent. Yield: 3 g (66%).

Workup

  1. temperaturewas heated to 120 deg C
  2. temperatureby heating at 120 deg C
  3. waitfor 2 h
  4. temperatureIt was cooled to RT
  5. washwas first washed with water (150 ml×3)
  6. dry with materialbrine, dried over sodium sulphate
  7. concentrationconcentrated under vacuum
  8. customColumn purified over 230-400 Silica gel (flash)

Sources & evidence

ORD record
ord-f5fd3821459c416c945e3d498ee910f1
Source dataset
uspto-grants-2015_11
Patent number
US09181240B2

Reaction notes

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