Sodium hydride → 1-(3,4-dimethoxyphenyl)-2-(3,9-dimethyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)ethanol

HRID 1045626Notes

Reaction equation

HRID 1045626 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:13]2[C:12]3[CH:11]=[C:10]([CH3:16])[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:4][CH2:3]1.[H-].[Na+].[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:29]2[CH2:31][O:30]2)[CH:24]=[CH:25][C:26]=1[O:27][CH3:28]>CN(C=O)C>[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:29]([OH:30])[CH2:31][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:16])=[CH:11][C:12]=3[C:13]3[CH2:14][CH2:15][N:2]([CH3:1])[CH2:3][CH2:4][C:5]2=3)[CH:24]=[CH:25][C:26]=1[O:27][CH3:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 104197742-(3,4-Dimethoxyphenyl)oxiraneHCID 685600921,2,3,4,5,6-Hexahydro-3,9-dimethylazepino[4,5-b]indole

Product 1

HCID 593683171-(3,4-dimethoxyphenyl)-2-(3,9-dimethyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)ethanolYield 5.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3,9-Dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (500 mg, 2.33 mmol) was dissolved in DMF (6 ml). A solution of sodium hydride (50%) (168 mg, 7.00 mmol) was added in portions at RT and stirred at RT for 10 min. A solution of 2-(3,4-dimethoxyphenyl)oxirane (630 mg, 3.50 mmol) in DMF (4 ml) was added dropwise for 10 min and stirred for 14 h at RT. Reaction was monitored by LCMS. The reaction mixture was quenched with ice water, extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography to get 50 mg of pure product. 1H NMR (CDCl3, Oxalate salt) δ (ppm): 7.40-7.30 (m, 2H), 7.10-7.00 (m, 1H), 6.90-6.80 (t, 2H), 6.80-6.60 (t, 1H), 5.00-4.80 (t, 2H), 4.30-4.20 (m, 2H), 3.95 (s, 3H), 3.80 (s, 3H), 3.00-2.90 (m, 4H), 2.80 (s, 3H), 2.75-2.70 (m, 2H), 2.35 (s, 3H).

Workup

  1. stirringstirred for 14 h at RT
  2. customReaction
  3. customThe reaction mixture was quenched with ice water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated under reduced pressure
  8. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-998b7e3d76fd4381945624afce012276
Source dataset
uspto-grants-2013_10
Patent number
US08569287B2

Reaction notes

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