Cesium carbonate → 4-[2-(4'-Fluoro-biphenyl-4-yloxy)-acetylamino]-thiophene-3-carboxylic acid methyl ester

HRID 14590

Reaction equation

HRID 14590 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](I)=[CH:16][CH:15]=2)=[CH:8][S:7][CH:6]=1)=[O:4].[F:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.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:26]3[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=3)=[CH:16][CH:15]=2)=[CH:8][S:7][CH:6]=1)=[O:4]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 2856454-Fluorophenylboronic acidHCID 686873304-[2-(4-Iodo-phenoxy)-acetylamino]-thiophene-3-carboxylic acid methyl ester

Product 1

HCID 686873364-[2-(4'-Fluoro-biphenyl-4-yloxy)-acetylamino]-thiophene-3-carboxylic acid methyl esterYield 124.3%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
80 °C

Procedure

To a solution of 4-[2-(4-iodo-phenoxy)-acetylamino]-thiophene-3-carboxylic acid methyl ester (0.1 g, 0.428 mmol) in a mixture of tetrahydrofuran (21 mL) and water (5 mL) was added 4-fluorophenylboronic acid (40.3 mg, 0.288 mmol) and cesium carbonate (313 mg, 0.96 mmol). The solution was then degassed by bubbling a flux of argon for 20 minutes before adding polymer bound tetrakis(triphenylphosphine)palladium (Aldrich-511579, 12.86 mg, 0.009 mmol). The reaction mixture was then stirred for 90 min 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 brine and dried over sodium sulfate before being concentrated in vacuo. The residue was then filtered through a pad of silica (SiO2, EtOAc, 100%) to yield the title compound as a light brown solid (138 mg, 99%).

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 brine
  6. dry with materialdried over sodium sulfate
  7. concentrationbefore being concentrated in vacuo
  8. filtrationThe residue was then filtered through a pad of silica (SiO2, EtOAc, 100%)

Sources & evidence

ORD record
ord-8a2483aa85a646cbbd1dd630a3ffbad5
Source dataset
uspto-grants-2010_06
Patent number
US07732452B2

Linked notes

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