Potassium Carbonate → 2-(2-{4-[1-(2-Thiophen-3-yl-ethyl)-1h-indol-3-yl]-piperidin-1-yl}-ethoxy)-benzoic acid

HRID 457784

Reaction equation

HRID 457784 reaction equation
C[O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][CH2:11][CH2:12]Cl.[NH:15]1[CH2:20][CH2:19][CH:18]([C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]([CH2:30][CH2:31][C:32]3[CH:36]=[CH:35][S:34][CH:33]=3)[CH:22]=2)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+]>CC(CC(C)C)=O>[S:34]1[CH:35]=[CH:36][C:32]([CH2:31][CH2:30][N:23]2[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:21]([CH:18]3[CH2:19][CH2:20][N:15]([CH2:12][CH2:11][O:10][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[C:3]([OH:2])=[O:14])[CH2:16][CH2:17]3)=[CH:22]2)=[CH:33]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 9837283Methyl 2-(2-chloroethoxy)benzoateHCID 179643093-piperidin-4-yl-1-(2-thiophen-3-yl-ethyl)-1H-indole

Product 1

HCID 102991632-(2-{4-[1-(2-Thiophen-3-yl-ethyl)-1h-indol-3-yl]-piperidin-1-yl}-ethoxy)-benzoic acidYield 99.3%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent2×

Procedure

A solution of 1.5 g (0.007 mol) of 2-(2-chloro-ethoxy)-benzoic acid methyl ester (prepared in Example 1, part C) in 5 mL of methyl-iso-butylketone was added to a suspension of 2 g (0.065 mol) of 3-piperidin-4-yl-1-(2-thiophen-3-yl-ethyl)-1H-indole and 1.8 g (0.013 mol) of potassium carbonate in 45 mL of methyl-iso-butylketone. The reaction mixture was refluxed for 18 h. The crude mixture was filtered to remove inorganic salts and the solvent was removed under reduced pressure affording 3.3 g of a crude oil. The crude mixture was purified by flash chromatography over silica gel affording 1.5 g (48% of yield) of 2-(2-{4-[1-(2-thiophen-3-yl-ethyl)-1H-indol-3-yl]-piperidin-1-yl}-ethoxy)-benzoic acid methyl ester. This ester was dissolved in a mixture of 25 mL of methanol/THF 3:2 and hydrolysed with 2N NaOH at room temperature for 16 hours. The crude mixture was neutralised with 2N HCl aqueous solution and the solvent was removed under reduced pressure. The crude residue was precipitated with dichloromethane and then recrystallised with methanol affording 1.3 g of the expected acid.

Workup

  1. temperatureThe reaction mixture was refluxed for 18 h
  2. filtrationThe crude mixture was filtered
  3. customto remove inorganic salts
  4. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c8dcbf749605476c9a31163e2cfcb193
Source dataset
uspto-grants-2007_03
Patent number
US07189741B2

Linked notes

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