Potassium Carbonate → {4'-Bromo-2'-[(tert-butoxycarbonyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid ethyl ester

HRID 1625665Notes

Reaction equation

HRID 1625665 reaction equation
[C:1]([O:5][C:6](=[O:19])[N:7]([CH2:10][C:11]1[CH:16]=[C:15]([Br:17])[CH:14]=[CH:13][C:12]=1I)[CH2:8][CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH2:20]([O:22][C:23](=[O:42])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=1)[CH3:21].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.ClCCl.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>[CH2:20]([O:22][C:23](=[O:42])[CH2:24][C:25]1[CH:26]=[C:27]([C:12]2[CH:13]=[CH:14][C:15]([Br:17])=[CH:16][C:11]=2[CH2:10][N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:19])[CH2:8][CH3:9])[C:28]([O:31][CH3:32])=[CH:29][CH:30]=1)[CH3:21]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 58120060[4-Methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl esterHCID 58149219tert-Butyl 5-bromo-2-iodobenzyl(ethyl)carbamate

Product 1

HCID 58148864{4'-Bromo-2'-[(tert-butoxycarbonyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid ethyl ester

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

(5-Bromo-2-iodo-benzyl)-ethyl-carbamic acid tert-butyl ester (2.0 g, 4.54 mmol), [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (1.67 g, 5.21 mmol), and potassium carbonate (1.57 g, 11.4 mmol) were combined in DME:H2O (2:1) under nitrogen. The mixture was purged with nitrogen, and then tetrakis(triphenylphosphine)palladium(0) (0.150 g, 0.13 mmol) was added, and the reaction was heated to 80° C. for 36 hours. Once no starting material was seen by analytical LCMS, the mixture was cooled to room temperature and diluted with dichloromethane and water. The aqueous layer was separated and extracted with dichloromethane, and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (0-100% ethyl acetate in hexanes) to give the title compound.

Workup

  1. customThe mixture was purged with nitrogen
  2. temperaturethe mixture was cooled to room temperature
  3. customThe aqueous layer was separated
  4. extractionextracted with dichloromethane
  5. dry with materialthe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2b227cb6d42e46f6949770c41322eb50
Source dataset
uspto-grants-2014_07
Patent number
US08785393B2

Reaction notes

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