Dimethylformamide → 3-(3-dimethylamino-propyl)-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde

HRID 1372394Notes

Reaction equation

HRID 1372394 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]1([CH3:22])[CH2:15][C:14]2[NH:13][CH:12]=[C:11]([CH2:16][CH2:17][CH2:18][N:19]([CH3:21])[CH3:20])[C:10]=2[CH2:9][CH2:8]1.[OH-].[K+].CN(C)[CH:27]=[O:28]>>[CH3:20][N:19]([CH3:21])[CH2:18][CH2:17][CH2:16][C:11]1[C:10]2[CH2:9][CH2:8][C:7]([CH3:22])([CH3:6])[CH2:15][C:14]=2[NH:13][C:12]=1[CH:27]=[O:28]

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 14797Potassium HydroxideHCID 24813Phosphorus oxychlorideHCID 18624233[3-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indol-3-yl)-propyl]-dimethyl-amine

Product 1

HCID 225710703-(3-dimethylamino-propyl)-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde

Procedure

Phosphorus oxychloride (0.5 mL, 5.1 mmol) was added dropwise to ice-cooled dimethylformamide (1.1 mL, 14.1 mmol) and then stirred at room temperature for 30 minutes. A solution of [3-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indol-3-yl)-propyl]-dimethyl-amine (1.1 g, 4.6 mmol) in dimethylformamide (2 mL) was added dropwise at −5° C. The mixture was stirred at room temperature overnight. Ice cubes were added to the reaction mixture followed by the addition of 10 N potassium hydroxide to pH 11–12 and stirring for one hour. The mixture was extracted with ethyl acetate and the extract washed with brine and concentrated. The residue was chromatographed (5%-10% methanol in dichloromethane) to give 650 mg of 3-(3-dimethylamino-propyl)-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde as a brown solid. 1H-NMR (360 MHz, dimethylsulfoxide-d6) δ 11.25 (br s, 1H, NH), 9.41 (s, 1H, CHO), 2.62 (t, 2H, CH2), 2.36 (t, 2H, CH2), 2.30 (s, 2H, CH2), 2.21 (t, 2H, CH2), 2.12 (s, 6H, 2×CH3), 1.60 (m, 2H, CH2), 1.46 (t, 2H, CH2), 0.93 (s, 6H, 2×CH3). MS m/z 262 [M+].

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. additionIce cubes were added to the reaction mixture
  3. stirringstirring for one hour
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe extract washed with brine
  6. concentrationconcentrated
  7. customThe residue was chromatographed (5%-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-17923d3e1fed4a2590543d790ae86712
Source dataset
uspto-grants-2007_01
Patent number
US07157577B2

Reaction notes

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