Water → {4'-Bromo-2'-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid ethyl ester

HRID 1625674Notes

Reaction equation

HRID 1625674 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([CH:16]=1)[CH2:7][N:8]([CH2:14][CH3:15])[C:9]([CH:11]1[CH2:13][CH2:12]1)=[O:10].[CH2:18]([O:20][C:21](=[O:40])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=1)[CH3:19].C(=O)([O-])[O-].[K+].[K+].O>COCCOC.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>[CH2:18]([O:20][C:21](=[O:40])[CH2:22][C:23]1[CH:24]=[C:25]([C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:16][C:6]=2[CH2:7][N:8]([C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])[CH2:14][CH3:15])[C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)[CH3:19]

Participants

7

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 58149034Cyclopropanecarboxylic acid(5-bromo-2-iodo-benzyl)-ethyl-amide

Product 1

HCID 58149020{4'-Bromo-2'-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

Cyclopropanecarboxylic acid (5-bromo-2-iodo-benzyl)-ethyl-amide (6.0 g, 14.7 mmol), [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (5.2 g, 16.2 mmol), and potassium carbonate (5.09 g, 36.8 mmol) were combined in DME (50 mL) and water (20 mL) under nitrogen. The mixture was purged with nitrogen, and then tetrakis(triphenylphosphine)palladium(0) (0.85 g, 0.74 mmol) was added, and the reaction was heated to 75° C. The reaction was monitored by analytical LCMS and an additional portion of the boronic ester (0.500 g, 1.56 mmol) was added to push the reaction to completion. When the starting material was consumed, the mixture was cooled to room temperature and diluted with ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate, and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (0-25% ethyl acetate in hexanes) to give the title compound.

Workup

  1. customThe mixture was purged with nitrogen
  2. customthe reaction to completion
  3. customWhen the starting material was consumed
  4. temperaturethe mixture was cooled to room temperature
  5. additiondiluted with ethyl acetate and water
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate
  8. dry with materialthe combined organic layers were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel chromatography (0-25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-efe76110a2b7448eb71b6cbb9243f859
Source dataset
uspto-grants-2014_07
Patent number
US08785393B2

Reaction notes

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