Potassium Carbonate → Methyl 3'-amino-4'-chloro-2-methylbiphenyl-4-carboxylate

HRID 2093194Notes

Reaction equation

HRID 2093194 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[Cl:8].Br[C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=1[CH3:23].C(=O)([O-])[O-].[K+].[K+]>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].CC(C)=O>[NH2:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=2[CH3:23])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 3294148Methyl 4-bromo-3-methylbenzoateHCID 43416433-Amino-4-chlorophenylboronic acid

Product 1

HCID 57704763Methyl 3'-amino-4'-chloro-2-methylbiphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 180AcetoneSolvent

Conditions

Temperature
70 °C

Procedure

(3-amino-4-chlorophenyl)boronic acid (1.0 g, 5.834 mmol), methyl 4-bromo-3-methylbenzoate (1.337 g, 5.834 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (476 mg, 0.583 mmol), aqueous potassium carbonate (11.57 mL, 1M, 11.57 mmol) and acetone (53 mL) were mixed and heated in a 70° C. oil bath for 1.5 hours to complete the coupling. Volatiles were removed from the crude mixture under reduced pressure. The resulting mixture was treated with water followed by ethyl acetate extraction. The combined extracts were dried over Na2SO4, filtrated and concentrated under reduced pressure to afford a dark oil. The resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge, 0-40% EtOAc in hexanes) to afford methyl 3′-amino-4′-chloro-2-methylbiphenyl-4-carboxylate. LCMS calc.=275.07; found=276.23 (M+1)+.

Workup

  1. customVolatiles were removed from the crude mixture under reduced pressure
  2. additionThe resulting mixture was treated with water
  3. extractionfollowed by ethyl acetate extraction
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfiltrated
  6. concentrationconcentrated under reduced pressure
  7. customto afford a dark oil
  8. customThe resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge, 0-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-67aef0a0370c429cb069a7515bf4a817
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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