Sodium Carbonate → (1R)-1-(3',5'-dinitrobiphenyl-4-yl)-2,2-difluoroethanol

HRID 530400Notes

Reaction equation

HRID 530400 reaction equation
Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1.[F:14][CH:15]([F:27])[C@@H:16]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)[OH:17].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[N+:11]([C:4]1[CH:3]=[C:2]([C:21]2[CH:20]=[CH:19][C:18]([C@@H:16]([OH:17])[CH:15]([F:27])[F:14])=[CH:23][CH:22]=2)[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=1)([O-:13])=[O:12]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 445341-Bromo-3,5-dinitrobenzeneHCID 129321749{4-[(1R)-2,2-difluoro-1-hydroxyethyl]phenyl}boronic acid

Product 1

HCID 118307608(1R)-1-(3',5'-dinitrobiphenyl-4-yl)-2,2-difluoroethanol

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 1-bromo-3,5-dinitrobenzene (5 g, 19.6 mmol), PdCl2(dppf)-dichloromethane adduct (0.802 g, 0.982 mmol), {4-[(1R)-2,2-difluoro-1-hydroxyethyl]phenyl}boronic acid (4.36 g, 21.6 mmol), and aqueous sodium carbonate (2 M, 29.5 mL, 58.9 mmol) in dioxane (65.6 mL) was degassed by sparging with nitrogen. The mixture was heated to 85° C. for 2 hours, and then allowed to cool to room temperature. The mixture was diluted with water, extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes) to give (1R)-1-(3′,5′-dinitrobiphenyl-4-yl)-2,2-difluoroethanol as an off-white solid. MS ESI calc'd. for C14H9F2N2O4[M+H−H2O]+ 307, found 307.

Workup

  1. customwas degassed
  2. customby sparging with nitrogen
  3. temperatureto cool to room temperature
  4. additionThe mixture was diluted with water
  5. extractionextracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-94b656cdf2a84dd1b49eb422c18933f2
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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