Sodium Carbonate → [2'-(1-tert-Butoxycarbonylamino-ethyl)-5'-(pyridin-4-ylcarbamoyl)-biphenyl-3-yloxy]-acetic acid

HRID 1403668Notes

Reaction equation

HRID 1403668 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=[O:24])[NH:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:12][C:11]=1Br)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[C:27]([O-:30])([O-])=[O:28].[Na+].[Na+].[C:33]1(C)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[CH2:40]([OH:42])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>[C:1]([O:5][C:6]([NH:7][CH:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=[O:24])[NH:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:12][C:11]=1[C:35]1[CH:36]=[CH:37][CH:38]=[C:33]([O:42][CH2:40][C:27]([OH:30])=[O:28])[CH:34]=1)[CH3:9])=[O:26])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 21863594Toluene ethanolHCID 67408319{1-[2-Bromo-4-(pyridine-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 67409175[2'-(1-tert-Butoxycarbonylamino-ethyl)-5'-(pyridin-4-ylcarbamoyl)-biphenyl-3-yloxy]-acetic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To a solution of {1-[2-Bromo-4-(pyridine-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester (0.48 g) in a mixture of toluene/ethanol: 5/3 (12 ml) were added 3-phenoxy-acetic acid benzyl ester boronic acid (2 eq.), a solution of Na2CO3 (4 eq.) in water (4 ml) and Pd tetrakis (0.06 eq.). The reaction mixture was heated under reflux conditions for 2 hours. The reaction mixture was cooled to RT and filtered over celite. The celite residue was washed with EtOAc and EtOH. The solvent was removed under reduced pressure and the residue was taken up in DCM. The precipitate was filtered, washed with DCM and dried. The compound was purified by column chromatography (silicagel, DCM/MeOH gradient).

Workup

  1. temperatureThe reaction mixture was heated under reflux conditions for 2 hours
  2. filtrationfiltered over celite
  3. washThe celite residue was washed with EtOAc and EtOH
  4. customThe solvent was removed under reduced pressure
  5. filtrationThe precipitate was filtered
  6. washwashed with DCM
  7. customdried
  8. customThe compound was purified by column chromatography (silicagel, DCM/MeOH gradient)

Sources & evidence

ORD record
ord-ccb5d0d4b7c544edaa7a45b77fc71473
Source dataset
uspto-grants-2014_12
Patent number
US08912209B2

Reaction notes

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