Potassium Iodide → 4-{4-[2-(2-Butylpyridinylamino)ethoxy]phenyl}butanoic acid

HRID 1881033Notes

Reaction equation

HRID 1881033 reaction equation
CO[C:3](=O)[CH2:4][CH2:5][CH2:6]C1C=CC(OCCBr)=CC=1.C(N[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)CCC.[I-].[K+].C[O:32][C:33](=[O:57])[CH2:34][CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][N:46](C(CC)C)C2C=CC=CN=2)=[CH:39][CH:38]=1.[OH-].[Na+]>O1CCCC1.CO.C(OCC)(=O)C.C(N(CC)CC)C>[CH2:3]([C:23]1[C:28]([NH:46][CH2:45][CH2:44][O:43][C:40]2[CH:39]=[CH:38][C:37]([CH2:36][CH2:35][CH2:34][C:33]([OH:57])=[O:32])=[CH:42][CH:41]=2)=[CH:27][CH:26]=[CH:25][N:24]=1)[CH2:4][CH2:5][CH3:6]

Participants

10

Reactant 5

HCID 4875Potassium IodideHCID 14798Sodium HydroxideHCID 14322668N-Butyl-2-pyridinamine2×HCID 251578524-(4-(2-Bromoethoxy)phenyl)butanoic acid methyl esterHCID 672995864-{4-[2-(2-Butyl(pyridin-2-yl)amino)ethoxy]phenyl}butanoic acid methyl ester

Product 1

HCID 672998564-{4-[2-(2-Butylpyridinylamino)ethoxy]phenyl}butanoic acidYield 11%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(4-(2-bromoethoxy)phenyl)butanoic acid methyl ester (3) (956 mg) from Step 3, and N-butylpyridine-2-amine (4) (1.4 g) from Step 4, were dissolved in tetrahydrofuran (6 mL), then triethylamine (0.88 mL) and potassium iodide (530 mg) were added, and refluxed overnight by heating. Ethyl acetate (100 mL) was added to the reaction solution, and the organic layer was washed with water (100 mL) and saturated sodium chloride solution (50 mL). After drying on anhydrous sodium sulfate, filtration and vacuum concentration, the residue was purified by silica gel flash column chromatography (developing solvent: n-hexane:ethyl acetate=6:1) to give a mixture of 4-{4-[2-(2-butyl(pyridin-2-yl)amino)ethoxy]phenyl}butanoic acid methyl ester and N-butylpyridine-2-amine (4). This mixture was dissolved in methanol (4 mL) and tetrahydrofuran (4 mL), 2N sodium hydroxide aqueous solution (1 mL) was added, then stirred overnight at room temperature. The reaction solution was concentrated with 2N hydrochloric acid (1.1 mL), then the residue was purified by silica gel flash column chromatography (developing solvent: n-hexane:ethyl acetate=1:1) to give the above-identified compound (128 mg, yield 11%) as a colorless oil.

Workup

  1. temperaturerefluxed overnight
  2. temperatureby heating
  3. washthe organic layer was washed with water (100 mL) and saturated sodium chloride solution (50 mL)
  4. dry with materialAfter drying on anhydrous sodium sulfate, filtration and vacuum concentration
  5. customthe residue was purified by silica gel flash column chromatography (developing solvent: n-hexane:ethyl acetate=6:1)
  6. customto give
  7. concentrationThe reaction solution was concentrated with 2N hydrochloric acid (1.1 mL)
  8. customthe residue was purified by silica gel flash column chromatography (developing solvent: n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-b21391d705584a27b351a315529ba71c
Source dataset
uspto-grants-2012_11
Patent number
US08318781B2

Reaction notes

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