Triethylamine → 5-(2-hydroxy-ethyl)-2-trifluoromethyl-1H-indole-3-carboxylic Acid Benzyl Ester

HRID 966480Notes

Reaction equation

HRID 966480 reaction equation
[CH2:1]([O:8][C:9](=[O:27])/[CH:10]=[C:11](/[NH:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][OH:25])=[CH:19][C:18]=1I)\[C:12]([F:15])([F:14])[F:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[CH2:1]([O:8][C:9]([C:10]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH2:23][CH2:24][OH:25])[CH:21]=2)[NH:16][C:11]=1[C:12]([F:15])([F:14])[F:13])=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 23393858(E)-4,4,4-Trifluoro-3-[4-(2-hydroxy-ethyl)-2-iodo-phenylamino]-but-2-enoic Acid Benzyl Ester

Product 1

HCID 233938735-(2-hydroxy-ethyl)-2-trifluoromethyl-1H-indole-3-carboxylic Acid Benzyl EsterYield 6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of (E)-4,4,4-Trifluoro-3-[4-(2-hydroxy-ethyl)-2-iodo-phenylamino]-but-2-enoic acid benzyl ester (9.5 g, 19.3 mmol, 1.0 eq), Pd(OAc)2 (433 mg, 1.93 mmol, 0.1 eq), triethylamine (3.1 mL, 23.2 mmol, 1.2 eq), triphenyphosphinc (1.52 g, 5.79 mmol, 0.3 eq) and DMF (20 mL) was heated under refluxing in a 100-mL round bottom flask under nitrogen. The reaction mixture was stirred overnight. After the stirring was stopped, the mixture was partitioned between dichloromethane (100 mL) and water (100 mL) filtered through celite. The organic layer was washed with water (3×100 mL), dried over MgSO4, and concentrated. The crude residue was purified by flash chromatography (SiO2, hexanes-ethyl acetate) to yield 420 mg of the desired indole as pale yellow gel (6.0% yield).

Workup

  1. temperaturewas heated
  2. temperatureunder refluxing in a 100-mL round bottom flask under nitrogen
  3. customthe mixture was partitioned between dichloromethane (100 mL) and water (100 mL)
  4. filtrationfiltered through celite
  5. washThe organic layer was washed with water (3×100 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash chromatography (SiO2, hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-5188192e20e84dfba31babe9b5941208
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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