Sodium Carbonate → {1-[3'-Hydroxy-5-(pyridin-4-ylcarbamoyl)-biphenyl-2-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 2409366Notes

Reaction equation

HRID 2409366 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].[OH:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.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](=[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]=1[C:32]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:27])[CH:33]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 67408319{1-[2-Bromo-4-(pyridine-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 68245743{1-[3'-Hydroxy-5-(pyridin-4-ylcarbamoyl)-biphenyl-2-yl]-ethyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of {1-[2-bromo-4-(pyridine-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester (2087 μmol) and 3-hydroxyphenylboronic acid (1.55 eq) in a mixture of DME/EtOH:1/1 (8 ml) were added Na2CO3 (4 eq) and Pd tetrakis (0.05 eq.). The reaction mixture was flushed with Ar and was heated in the microwave at 130° C. for 1.5 hours. The reaction mixture was cooled to RT, diluted with 1N NaHCO3 and extracted with EtOAc. The organic layer was extracted with 1N NaHCO3 and the combined aqueous layers were acidified with citric acid and 1N HCl. The aqueous layer was extracted with EtOAc, the organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The compound was purified by recrystallization from EtOAc.

Workup

  1. customThe reaction mixture was flushed with Ar
  2. temperatureThe reaction mixture was cooled to RT
  3. additiondiluted with 1N NaHCO3
  4. extractionextracted with EtOAc
  5. extractionThe organic layer was extracted with 1N NaHCO3
  6. extractionThe aqueous layer was extracted with EtOAc
  7. dry with materialthe organic layer was dried over MgSO4
  8. customthe solvent was removed under reduced pressure
  9. customThe compound was purified by recrystallization from EtOAc

Sources & evidence

ORD record
ord-c8195834f72541f892c98e3806f9b93e
Source dataset
uspto-grants-2014_08
Patent number
US08815873B2

Reaction notes

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