Cesium carbonate → 4-[2-[5-(2-Methoxy-phenyl)-pyridin-2-yloxy]-acetylamino]-thiophene-3-carboxylic acid methyl ester

HRID 14596

Reaction equation

HRID 14596 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:9]([NH:10][C:11](=[O:21])[CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][N:15]=2)=[CH:8][S:7][CH:6]=1)=[O:4].[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:9]([NH:10][C:11](=[O:21])[CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[O:23][CH3:22])=[CH:16][N:15]=2)=[CH:8][S:7][CH:6]=1)=[O:4]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27339582-Methoxyphenylboronic acidHCID 686917104-[2-(5-Bromo-pyridin-2-yloxy)-acetylamino]-thiophene-3-carboxylic acid methyl ester

Product 1

HCID 686883444-[2-[5-(2-Methoxy-phenyl)-pyridin-2-yloxy]-acetylamino]-thiophene-3-carboxylic acid methyl esterYield 79%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-[2-(5-bromo-pyridin-2-yloxy)-acetylamino]-thiophene-3-carboxylic acid methyl ester (50 g, 0.135 mmol) in a mixture of tetrahydrofuran (10.5 mL) and water (2.5 mL) was added 2-methoxyphenylboronic acid (24.5 mg, 0.162 mmol) and cesium carbonate (175.3 mg, 0.54 mmol). The solution was then degassed by bubbling a flux of argon for 20 minutes before adding tetrakis(triphenylphosphine)palladium (4.24 mg, 0.0034 mmol). The reaction mixture was then stirred overnight at 80° C. under argon atmosphere before allowing to cool down to room temperature and diluting with ethyl acetate. The reaction mixture was then filtered; the filtrate was then washed twice with water and dried over sodium sulfate before being concentrated in vacuo. The residue was then purified by column chromatography (SiO2, EtOAc/Heptane, 0-60%) to yield the title compound as a light yellow solid (42.5 mg, 79%).

Workup

  1. customThe solution was then degassed
  2. customby bubbling a flux of argon for 20 minutes
  3. temperatureto cool down to room temperature
  4. filtrationThe reaction mixture was then filtered
  5. washthe filtrate was then washed twice with water
  6. dry with materialdried over sodium sulfate
  7. concentrationbefore being concentrated in vacuo
  8. customThe residue was then purified by column chromatography (SiO2, EtOAc/Heptane, 0-60%)

Sources & evidence

ORD record
ord-2a59fa4fb2cf49b090f85b7fa8e139dc
Source dataset
uspto-grants-2010_06
Patent number
US07732452B2

Linked notes

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