4-Aminophenylboronic acid → 3-(4'-Amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester

HRID 2427344Notes

Reaction equation

HRID 2427344 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([C:11](=[O:19])[C:12]2[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=2)[CH2:6]1)=[O:4].[NH2:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1>C1(C)C=CC=CC=1.O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([C:11]([C:12]2[CH:17]=[CH:16][C:15]([C:24]3[CH:25]=[CH:26][C:21]([NH2:20])=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)=[O:19])[CH2:6]1)=[O:4]

Participants

6

Reactant 2

HCID 27346154-Aminophenylboronic acidHCID 235493383-(4-Bromo-benzoyl)cyclohexanecarboxylic acid methyl ester

Product 1

HCID 235493393-(4'-Amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-(4-bromo-benzoyl)-cyclohexanecarboxylic acid methyl ester (500 mg, 1.54 mmol) and 4-aminophenyl boronic acid (252 mg, 1.85 mmol) in toluene (40 mL) and dioxane (10 mL), 2 N aqueous Na2CO3 (10 mL) was added, and the mixture was degassed by bubbling with a flow of argon for 45 minutes. (1,1-Bis(diphenylphosphino)ferrocene)-dichloropalladium (63 mg, 0.08 mmol) was added to the mixture, which was then heated at 80° C. overnight. The reaction mixture was cooled to rt, and then filtered through a pad of Celite®, rinsing with ethyl acetate. The organic layer was separated, washed with water and brine, and dried (Na2SO4). The solvent was removed by rotary evaporation, and the solid residue was purified by using a Biotage QuadUV flash chromatography system (eluant: 3:1 hexane/EtOAc). The product 3-(4′-amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester was obtained as a brown solid (200 mg, yield 38.5%). 1H NMR (300 MHz, DMSO) δ 7.90 (d, 2 H), 7.60 (d, 2 H), 7.45 (d, 2 H), 6.80 (d, 2 H), 3.70 (s, 3 H), 3.25 (m, 1 H), 2.50 (m, 1 H), 2.20-1.90 (m, 4 H), 1.70-1.50 (m, 4 H); LC-MS ret. time 3.80 min (method 2), m/z 338.17 (MH+).

Workup

  1. customthe mixture was degassed
  2. customby bubbling with a flow of argon for 45 minutes
  3. temperatureThe reaction mixture was cooled to rt
  4. filtrationfiltered through a pad of Celite®
  5. washrinsing with ethyl acetate
  6. customThe organic layer was separated
  7. washwashed with water and brine
  8. dry with materialdried (Na2SO4)
  9. customThe solvent was removed by rotary evaporation
  10. customthe solid residue was purified

Sources & evidence

ORD record
ord-f7b6538c851443228fe9eb318972cb52
Source dataset
uspto-grants-2011_06
Patent number
US07968576B2

Reaction notes

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