Triethylamine → 3-(4-{[4'-(2-Ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methoxy}-2-fluorophenyl)propanamide

HRID 273406Notes

Reaction equation

HRID 273406 reaction equation
[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][O:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30](O)=[O:31])=[C:24]([F:33])[CH:23]=3)[CH:15]=2)=[C:9]([CH3:34])[CH:8]=1)[CH3:2].N.CO.Cl.C([N:41]=C=NCCCN)C.ON1C2C=CC=CC=2N=N1.C1CCN2C(=NCCC2)CC1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C(#N)C>[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][O:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]([NH2:41])=[O:31])=[C:24]([F:33])[CH:23]=3)[CH:15]=2)=[C:9]([CH3:34])[CH:8]=1)[CH3:2]

Participants

9

Reactant 7

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 12905556HCID 12905556, compoundHCID 21705897Ammonia methanolHCID 574133733-(4-{[4'-(2-Ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methoxy}-2-fluorophenyl)propanoic acid

Product 1

HCID 589031103-(4-{[4'-(2-Ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methoxy}-2-fluorophenyl)propanamideYield 80%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-(4-{[4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-yl]methoxy}-2-fluorophenyl)propanoic acid (0.233 g, 0.500 mmol), 7 M ammonia/methanol (0.4 mL, 2.80 mmol) solution, 1-ethyl-3-(3-aminopropyl)carbodiimide hydrochloride (2.88 g, 1.50 mmol), 1-hydroxybenzotriazole (0.230 g, 1.50 mmol), 1,8-diazabicyclo[5.4.0]-7-undecene (0.448 mL, 3.00 mmol), triethylamine (0.502 mL, 3.60 mmol) and acetonitrile (3 mL) was stirred at room temperature for 27 hrs. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (50% ethyl acetate/hexane-ethyl acetate) to give the title compound (0.186 g, yield 80%) as a colorless oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by basic silica gel column chromatography (50% ethyl acetate/hexane-ethyl acetate)

Sources & evidence

ORD record
ord-3d1ae8904cff4f2b9eba5ff073760489
Source dataset
uspto-grants-2008_11
Patent number
US07456218B2

Reaction notes

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