Potassium Carbonate → 5-methoxy-3-[N-(4-(4-fluoro-phenyl)-4-oxo-butyl)-1,2,5,6-tetrahydro-pyridin-3-ylmethyl]-1H-indole

HRID 355992Notes

Reaction equation

HRID 355992 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][C:13]1[CH2:14][NH:15][CH2:16][CH2:17][CH:18]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:26][CH2:27][CH2:28][C:29]1([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)OCC[O:30]1>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][C:13]1[CH2:14][N:15]([CH2:26][CH2:27][CH2:28][C:29]([C:34]2[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=2)=[O:30])[CH2:16][CH2:17][CH:18]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27237782-(3-Chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolaneHCID 189408175-methoxy-3-(1,2,5,6-tetrahydro-pyridin-3-ylmethyl)-1H-indole

Product 1

HCID 98660505-methoxy-3-[N-(4-(4-fluoro-phenyl)-4-oxo-butyl)-1,2,5,6-tetrahydro-pyridin-3-ylmethyl]-1H-indole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of compound of Description 5 [5-methoxy-3-(1,2,5,6-tetrahydro-pyridin-3-ylmethyl)-1H-indole] (1.5 g; 0.0062 mol), potassium carbonate (4.3 g; 0.031 mol), KI (0.06 g; 0.0004 mol) and 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane (1.3 ml; 0.0064 mol) in dry dimethylformamide (30 ml) was heated at 80° C. for 6 hours. The reaction mixture was cool down to room temperature, quenched with water and then extracted with diethyl ether. The organic extract was dried (MgSO4) and evaporated under vacuum. The residue was taken up in a solution of hydrochloric acid (37%; 6 ml) in methanol (30 ml). The resulting mixture was stirred for 2 hours at room temperature. The reaction was then quenched with a saturated solution of aqueous sodium carbonate and the solvent (methanol) was evaporated under vacuum. The residual alkaline aqueous solution was extracted with methylene chloride. The organic extract was dried (MgSO4) and evaporated under vacuum. After purification by Flash Chromatography on silica gel using as eluent methylene chloride/methanol/ammonia (95/5/0,5), the desired compound was obtained (1,72 g). A solution of the compound in ethanol was saturated with gaseous hydrogen chloride. A white solid was precipitated. The title compound hydrochloride was collected by filtration, washed with ethanol and dried under vacuum.

Workup

  1. temperatureThe reaction mixture was cool down to room temperature
  2. customquenched with water
  3. extractionextracted with diethyl ether
  4. extractionThe organic extract
  5. dry with materialwas dried (MgSO4)
  6. customevaporated under vacuum
  7. customThe reaction was then quenched with a saturated solution of aqueous sodium carbonate
  8. customthe solvent (methanol) was evaporated under vacuum
  9. extractionThe residual alkaline aqueous solution was extracted with methylene chloride
  10. extractionThe organic extract
  11. dry with materialwas dried (MgSO4)
  12. customevaporated under vacuum
  13. customAfter purification by Flash Chromatography on silica gel using as eluent methylene chloride/methanol/ammonia (95/5/0,5)

Sources & evidence

ORD record
ord-7767533f33fc4763a658d91a72630a13
Source dataset
uspto-grants-1998_11
Patent number
US05834493

Reaction notes

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