Water → Rac-[1-(3,4-dichloro-phenyl)-2-(3-fluoro-3'-methanesulfonyl-biphenyl-4-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 384894Notes

Reaction equation

HRID 384894 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH:8]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=1)[C:9]([C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][C:12]=1[F:18])=[O:10])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].O.[CH3:34][S:35]([C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][CH:43]=1)(=[O:37])=[O:36]>C1(C)C=CC=CC=1.C(O)C.Cl[Pd]Cl>[C:1]([O:5][C:6](=[O:27])[NH:7][CH:8]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=1)[C:9]([C:11]1[CH:16]=[CH:15][C:14]([C:42]2[CH:41]=[CH:40][CH:39]=[C:38]([S:35]([CH3:34])(=[O:37])=[O:36])[CH:43]=2)=[CH:13][C:12]=1[F:18])=[O:10])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 68409235Rac-[2-(4-bromo-2-fluoro-phenyl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 68408670Rac-[1-(3,4-dichloro-phenyl)-2-(3-fluoro-3'-methanesulfonyl-biphenyl-4-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 21863594Toluene ethanolSolvent

Procedure

To a solution of 0.450 g (0.943 mmol) rac-[2-(4-bromo-2-fluoro-phenyl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester in 10.5 ml toluene/ethanol 19:1 were added 69 mg (0.094 mmol) PdCl2 (dppf), 0.238 g (2.83 mmol) sodium bicarbonate, 5 ml water and 212 mg (1.04 mmol) 3-methylsulfonylphenylboronic acid and the mixture heated to reflux for 18 h. The reaction mixture was cooled to ambient temperature, filtered through a Dicalite pad and the filtrated extracted with tertiary butyl methyl ether. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated. The crude product was purified by flash-chromatography over silica gel with a heptane/AcOEt gradient with 10-50% AcOEt: rac-[1-(3,4-dichloro-phenyl)-2-(3-fluoro-3′-methanesulfonyl-biphenyl-4-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester was obtained as colorless solid: MS (ISN): 550.2 and 552.2 (M−H)−.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 18 h
  3. filtrationfiltered through a Dicalite pad
  4. extractionthe filtrated extracted with tertiary butyl methyl ether
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by flash-chromatography over silica gel with a heptane/AcOEt gradient with 10-50% AcOEt

Sources & evidence

ORD record
ord-ae890604be0f43a5a61c90fd3ac30f26
Source dataset
uspto-grants-2013_02
Patent number
US08367838B2

Reaction notes

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