Sodium Carbonate → Methyl 5'-amino-2',4'-difluoro-2-methylbiphenyl-4-carboxylate

HRID 2093156Notes

Reaction equation

HRID 2093156 reaction equation
Br[C:2]1[C:3]([F:10])=[CH:4][C:5]([F:9])=[C:6]([CH:8]=1)[NH2:7].[CH3:11][C:12]1[CH:13]=[C:14]([CH:19]=[CH:20][C:21]=1B1OC(C)(C)C(C)(C)O1)[C:15]([O:17][CH3:18])=[O:16].C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(O)C>[NH2:7][C:6]1[C:5]([F:9])=[CH:4][C:3]([F:10])=[C:2]([C:21]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]=2[CH3:11])[CH:8]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27832955-Bromo-2,4-difluoroanilineHCID 110870242-Methyl-4-methoxycarbonylphenylboronic acid, pinacol ester2×

Product 1

HCID 57704793Methyl 5'-amino-2',4'-difluoro-2-methylbiphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 702EthanolSolvent

Procedure

5-bromo-2,4-difluoroaniline (500 mg, 2.40 mmol), methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (INTERMEDIATE 16, 797 mg, 2.88 mmol), sodium carbonate (2.40 mL, aq., 2M, 2.88 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (196 mg, 0.24 mmol) and ethanol (15 ml) were heated in an 80° C. oil bath for 3 hours then allowed to cool to ambient overnight. Volatiles were removed under reduced pressure. The pot residue was worked up w/DCM /brine/Na2SO4/filtration/concentration to afford a dark oil. The resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge). The column was eluted by a 0% to 40% EtOAc/hexanes gradient mixture. Related fractions were pooled and concentrated in vacuo to afford the title compound. LCMS (ESI) calc.=277.09; found=278.03 (M+1)+.

Workup

  1. temperatureto cool to ambient overnight
  2. customVolatiles were removed under reduced pressure
  3. concentrationw/DCM /brine/Na2SO4/filtration/concentration
  4. customto afford a dark oil
  5. customThe resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge)
  6. washThe column was eluted by a 0% to 40% EtOAc/hexanes gradient mixture
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5707c09f878f4e3f914fdee551062d5a
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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