Water → (4'-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-6-methoxy-biphenyl-3-yl)-acetic acid ethyl ester

HRID 2092415Notes

Reaction equation

HRID 2092415 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:10][C:11](=[O:26])[NH:12][C:13]1[C:14]([CH3:25])=[N:15][O:16][C:17]=1[C:18]1[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=1)[CH3:9].[CH2:27]([O:29][C:30](=[O:49])[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=1)[CH3:28].C(=O)([O-])[O-].[K+].[K+].O>COCCOC.CCOC(C)=O.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>[CH2:27]([O:29][C:30](=[O:49])[CH2:31][C:32]1[CH:33]=[C:34]([C:21]2[CH:22]=[CH:23][C:18]([C:17]3[O:16][N:15]=[C:14]([CH3:25])[C:13]=3[NH:12][C:11]([O:10][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH3:9])=[O:26])=[CH:19][CH:20]=2)[C:35]([O:38][CH3:39])=[CH:36][CH:37]=1)[CH3:28]

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 58120060[4-Methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl esterHCID 67350786[5-(4-Bromophenyl)-3-methylisoxazol-4-yl]carbamic acid 1-(2-chlorophenyl)ethyl ester

Product 1

HCID 67351947(4'-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-6-methoxy-biphenyl-3-yl)-acetic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid 1-(2-chloro-phenyl)-ethyl ester (0.100 g, 0.23 mmol) in DME (5 mL) was added [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (0.074 g, 0.23 mmol), followed by potassium carbonate (0.079 g, 0.58 mmol) and water (3 mL). The solution was purged with N2 for 10 minutes, and then tetrakis(triphenylphosphine)palladium(0) (0.027 g, 0.02 mmol) was added. The reaction was stirred at 100° C. until no starting material was seen by analytical LCMS and thin layer chromatography (tlc), and then cooled to room temperature and diluted with EtOAc. The mixture was extracted with EtOAc, and the combined organic layers were washed with water and brine. The combined aqueous layers were back-extracted with EtOAc, and the combined organic layers were dried and concentrated. The residue was purified by silica gel chromatography to give (4′-{4-[1-(2-chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-6-methoxy-biphenyl-3-yl)-acetic acid ethyl ester.

Workup

  1. customThe solution was purged with N2 for 10 minutes
  2. temperaturecooled to room temperature
  3. extractionThe mixture was extracted with EtOAc
  4. washthe combined organic layers were washed with water and brine
  5. extractionThe combined aqueous layers were back-extracted with EtOAc
  6. customthe combined organic layers were dried
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-c127f0756dd84aa1a79962b0885cd205
Source dataset
uspto-grants-2013_05
Patent number
US08440707B2

Reaction notes

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