Sodium hydride → 4-allyl-5-[2-(4-fluoro-phenyl)-allyl]-2,4,8-trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 576520Notes

Reaction equation

HRID 576520 reaction equation
[H-].[Na+].[CH2:3]([C:6]1([CH3:21])[C:11]2[NH:12][C:13]3[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][C:18]=3[C:10]=2[CH2:9][N:8]([CH3:20])[CH2:7]1)[CH:4]=[CH2:5].Br[CH2:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)=[CH2:25]>CN(C=O)C>[CH2:3]([C:6]1([CH3:21])[C:11]2[N:12]([CH2:25][C:24]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)=[CH2:23])[C:13]3[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][C:18]=3[C:10]=2[CH2:9][N:8]([CH3:20])[CH2:7]1)[CH:4]=[CH2:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 116942121-(3-Bromoprop-1-en-2-yl)-4-fluorobenzeneHCID 673559434-allyl-2,4,8-trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 673564374-allyl-5-[2-(4-fluoro-phenyl)-allyl]-2,4,8-trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 35.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of sodium hydride (0.236 g, 5.9 mmol) in dry DMF (5 mL) at 0° C. was added 4-allyl-2,4,8-trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1 g, 3.937 mol, in dry DMF 2 mL). After addition was complete, reaction mixture was stirred at 0° C. for an additional 10 min. 1-(1-Bromomethyl-vinyl)-4-fluoro-benzene (1.09 g, 5.118 mmol) in dry DMF (3 mL) was added dropwise at 0° C. The reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was diluted with ice-water and extracted with EtOAc (2×50 mL). The organic layer was repeatedly washed with water, dried over anhydrous sodium sulfate, concentrated under reduced pressure and the residue purified by chromatography on neutral aluminum oxide (eluting with EtOAc:Hexanes, 1:99) to obtain 700 mg of 4-allyl-5-[2-(4-fluoro-phenyl)-allyl]-2,4,8-trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole.

Workup

  1. additionAfter addition
  2. customreaction mixture
  3. stirringThe reaction mixture was stirred at 25° C. for 16 h
  4. extractionextracted with EtOAc (2×50 mL)
  5. washThe organic layer was repeatedly washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customthe residue purified by chromatography on neutral aluminum oxide (eluting with EtOAc:Hexanes, 1:99)

Sources & evidence

ORD record
ord-15e55457ec0a4b9dbf42cab2c48d1638
Source dataset
uspto-grants-2015_05
Patent number
US09040519B2

Reaction notes

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