5-Methoxy-2-methylindole → 4-(2-(5-Methoxy-2-methyl-1H-indol-3-YL)ethyl)morpholine

HRID 1733856Notes

Reaction equation

HRID 1733856 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[CH:6]2.C[Mg+].[Br-].I[CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>C1COCC1.C([O-])(O)=O.[Na+].[Cl-].[Cl-].[Zn+2]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1

Participants

7

Reactant 3

HCID 706425-Methoxy-2-methylindoleHCID 111491684-(2-iodoethyl)morpholineHCID 178418689HCID 178418689, compound

Product 1

HCID 194388094-(2-(5-Methoxy-2-methyl-1H-indol-3-YL)ethyl)morpholineYield 7%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To 5-methoxy-2-methyl-1H-indole (5.00 g; 31.0 mmol) in 30 mL of dry THF at 0° C. was added dropwise MeMgBr (3.0M in Et2O; 11.4 mL; 34.2 mmol). The solution was stirred 30 min at r.t. after which ZnCl2 (0.5M in THF; 64 mL; 32 mmol) was added. The mixture was stirred at r.t., after 1 h, N-(2-iodoethyl)morpholine (14.41 g; 51.5 mmol) was added. The final mixture was stirred at r.t. overnight. The mixture was poored in saturated NaHCO3 (100 mL), extracted with EtOAc (2×100 mL). The organic phase was washed with brine (100 mL), dried over Na2SO4, filtered, concentrated and flash chromatographed (Silica gel; EtOAc/Ace O to 10%) to yield 587 mg (7%) of the title compound.

Workup

  1. additionwas added
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe organic phase was washed with brine (100 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customflash chromatographed (Silica gel; EtOAc/Ace O to 10%)

Sources & evidence

ORD record
ord-6331567eb402415e913afdc0262b9613
Source dataset
uspto-grants-1996_07
Patent number
US05532237

Reaction notes

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