Diisopropylamine → Tert-butyl 5-(2,2-difluoro-1-hydroxyethyl)-2',4'-difluorobiphenyl-3-carboxylate

HRID 888412Notes

Reaction equation

HRID 888412 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([CH:15]([OH:19])[CH:16]([F:18])[F:17])[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[F:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=1B(O)O.C1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=1.[Na+].[Na+].[Na+].C(NC(C)C)(C)C>CN(C)C=O.O.[Cl-].[Na+].O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:17][CH:16]([F:18])[CH:15]([C:13]1[CH:12]=[C:4]([C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])[CH:3]=[C:2]([C:24]2[CH:23]=[CH:22][C:21]([F:20])=[CH:26][C:25]=2[F:27])[CH:14]=1)[OH:19]

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 27343342,4-Difluorophenylboronic acidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 68501370Tert-butyl 3-bromo-5-(2,2-difluoro-1-hydroxyethyl)benzoate

Product 1

HCID 68500331Tert-butyl 5-(2,2-difluoro-1-hydroxyethyl)-2',4'-difluorobiphenyl-3-carboxylateYield 93.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of tert-butyl 3-bromo-5-(2,2-difluoro-1-hydroxyethyl)benzoate (1.0 g, 2.97 mmol) in N,N-dimethylformamide (11.9 mL) and water (2.97 mL) was added (2,4-difluorophenyl)boronic acid (0.61 g, 3.86 mmol), palladium(II) acetate (67 mg, 0.3 mmol), 3,3′3″-phosphinidynetris(benzenesulfonic acid)trisodium salt (0.51 g, 0.89 mmol) and diisopropylamine (1.27 mL, 8.9 mmol). The mixture was stirred at ambient temperature. After 1 h, brine was added and mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→60% hexanes/ethyl acetate) gave the title compound (1.03 g). MS 315.0 (M-t-butyl group).

Workup

  1. extractionmixture was extracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (100% hexanes→60% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-7f6c911bbcf449bda699d8835a279541
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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