Sodium Carbonate → 3-Fluoro[1,1'-biphenyl]-2-amine

HRID 2276730Notes

Reaction equation

HRID 2276730 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[C:17]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:18]=1[NH2:19].C([O-])=O.[NH4+]>O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC#N.O>[F:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:17]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:18]=1[NH2:19]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 2723923Ammonium formateHCID 27829402-Bromo-6-fluoroaniline

Product 1

HCID 463146263-Fluoro[1,1'-biphenyl]-2-amine

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
50 °C

Procedure

To a solution of Na2CO3 (1.116 g, 10.53 mmol) in water (15 ml) was added poly(ethylene glycol) 2000 (17 g, 5.26 mmol) followed by palladium(II) acetate (0.024 g, 0.105 mmol). The suspension was heated to 50° C. Once the mixture became clear, phenylboronic acid (0.963 g, 7.89 mmol) followed by 2-bromo-6-fluoroaniline (1 g, 5.26 mmol) were added and heated at 120° C. for 30 min. The mixture was cooled, diluted with EtOAc, washed with water, dried and concentrated. The crude material was purified by ISCO (24 g REDISEP® silica column, gradient elution, 0-15% ethyl acetate in hexanes) to give Preparation 5A (800 mg, 81%): LCMS: HPLC: RT=2.016 min (MeCN/H2O with HCOONH4, Ascentis Express C8 2.7 μm 5×2.1 mm, gradient=4 min, wavelength=220 nm); MS(ES): m/z=188 [M+H]+; 1H NMR (CDCl3) δ 7.43-7.48 (m, 4H), 7.35-7.40 (m, 1H), 6.97-7.02 (m, 1H), 6.92 (dt, J=7.6, 1.2 Hz, 1H), 6.71-6.77 (m, 1H), 3.82 (br s, 2H).

Workup

  1. additionwere added
  2. temperatureheated at 120° C. for 30 min
  3. temperatureThe mixture was cooled
  4. washwashed with water
  5. customdried
  6. concentrationconcentrated
  7. customThe crude material was purified by ISCO (24 g REDISEP® silica column, gradient elution, 0-15% ethyl acetate in hexanes)
  8. customto give

Sources & evidence

ORD record
ord-e8ef268d8c3941569d58a87e702ce06f
Source dataset
uspto-grants-2015_09
Patent number
US09133126B2

Reaction notes

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