Potassium Carbonate → 4'-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-biphenyl-4-carboxylic acid

HRID 553671Notes

Reaction equation

HRID 553671 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:34])[NH:12][C:13]1[C:14]([CH3:33])=[N:15][O:16][C:17]=1[C:18]1[CH:23]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][CH:19]=1)[CH3:9].Br[C:36]1[CH:44]=[CH:43][C:39]([C:40]([OH:42])=[O:41])=[CH:38][CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:10][C:11]([NH:12][C:13]1[C:14]([CH3:33])=[N:15][O:16][C:17]=1[C:18]1[CH:23]=[CH:22][C:21]([C:36]2[CH:44]=[CH:43][C:39]([C:40]([OH:42])=[O:41])=[CH:38][CH:37]=2)=[CH:20][CH:19]=1)=[O:34])[CH3:9]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 114644-Bromobenzoic acidHCID 67350448{3-Methyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-isoxazol-4-yl}-carbamic acid 1-(2-chloro-phenyl)-ethyl ester

Product 1

HCID 462399064'-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-biphenyl-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

{3-Methyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-isoxazol-4-yl}-carbamic acid 1-(2-chloro-phenyl)-ethyl ester (0.100 g, 0.21 mmol), 4-bromobenzoic acid (0.042 g, 0.21 mmol), and potassium carbonate (0.073 g, 0.53 mmol) were combined in DME (10 mL) and water (5 mL). The solution was purged with N2 for 10 minutes, and then (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (0.014 g, 0.02 mmol) was added. The reaction was stirred at 70° C. overnight, until no starting material was seen by analytical LCMS. The mixture was cooled to room temperature and quenched with water. The mixture was extracted with EtOAc, and the combined organic layers were dried and concentrated. The residue was purified by preparative HPLC to give the title compound.

Workup

  1. customThe solution was purged with N2 for 10 minutes
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched with water
  4. extractionThe mixture was extracted with EtOAc
  5. customthe combined organic layers were dried
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-f43a6eeec0f143c28023c4efcba91f98
Source dataset
uspto-grants-2011_11
Patent number
US08048902B2

Reaction notes

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