Potassium Hydroxide → 4-(2-(6-methoxy-2-methyl-1H-indol-1-yl)ethyl)morpholine

HRID 574612Notes

Reaction equation

HRID 574612 reaction equation
Cl.Cl[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[OH-].[K+].[CH3:13][O:14][C:15]1[CH:23]=[C:22]2[C:18]([CH:19]=[C:20]([CH3:24])[NH:21]2)=[CH:17][CH:16]=1>CS(C)=O>[CH3:13][O:14][C:15]1[CH:23]=[C:22]2[C:18]([CH:19]=[C:20]([CH3:24])[N:21]2[CH2:3][CH2:4][N:5]2[CH2:10][CH2:9][O:8][CH2:7][CH2:6]2)=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 108447096-methoxy-2-methyl-1H-indole

Product 1

HCID 667645524-(2-(6-methoxy-2-methyl-1H-indol-1-yl)ethyl)morpholine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a solution of 2-chloroethylmorpholine HCl (138 mg, 0.74 mmol) in 0.3 mL DMSO was added pulverized KOH (104 mg, 1.86 mmol), then after 10 min, a solution of 6-methoxy-2-methylindole (138 mg, 0.74 mmol) in 0.2 mL DMSO was added and the reaction stirred at room temperature overnight. The reaction mixture was partitioned between H2O and toluene, and the organic extract washed two times with H2O, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified via silica gel chromatography using a gradient from 0 to 10% MeOH in CH2Cl2 to give a final yield of 17 mg (0.062 mmol). 1H NMR (500 MHz, CDCl3, δ): 2.45 (s, 3H), 2.50-2.63 (m, 4H), 2.67 (t, J=7.4 Hz, 2H), 3.71-3.83 (m, 4H), 3.90 (s, 3H), 4.18 (t, J=7.4 Hz, 2H), 6.19 (s, 1H), 6.78 (dd, J=8.5 Hz, 2.2 Hz, 1H), 6.81 (s, 1H), 7.42 (d, J=8.5 Hz, 1H). 13C NMR (500 MHz, CDCl3, δ): 12.77, 40.98, 54.13, 55.92, 57.74, 66.94, 93.50, 99.82, 108.35, 120.26, 122.51, 135.31, 137.25, 155.53. MS m/z 275.3 [M+H]+.

Workup

  1. customThe reaction mixture was partitioned between H2O and toluene
  2. extractionthe organic extract
  3. washwashed two times with H2O
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified via silica gel chromatography
  8. customto give a final yield of 17 mg (0.062 mmol)

Sources & evidence

ORD record
ord-653b3416b18c4e5b886d1d1196b6c569
Source dataset
uspto-grants-2015_05
Patent number
US09034895B2

Reaction notes

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