Potassium Carbonate → 3-(3'-Carbamoyl-biphenyl-4-yloxymethyl)-benzoic acid

HRID 2113003Notes

Reaction equation

HRID 2113003 reaction equation
C[O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][CH:13]=2)[CH:5]=1.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+].[NH2:32][C:33]([C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1)=[O:34]>O>[C:33]([C:35]1[CH:40]=[C:39]([C:15]2[CH:16]=[CH:17][C:12]([O:11][CH2:10][C:6]3[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=3)[C:3]([OH:2])=[O:19])=[CH:13][CH:14]=2)[CH:38]=[CH:37][CH:36]=1)(=[O:34])[NH2:32]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2737814(3-Carbamoylphenyl)boronic acidHCID 57643351Methyl 3-((4-iodophenoxy)methyl)benzoate2×

Product 1

HCID 115810393-(3'-Carbamoyl-biphenyl-4-yloxymethyl)-benzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A first stock solution was prepared consisting of 3-(4-iodo-phenoxymethyl)-benzoic acid methyl ester (of Intermediate 1; 1.11 g, 3 mmol), bis(tri-cyclohexyl-phosphine)palladium (available from Strem Chemicals, Inc., Newburyport, Mass.; 105 mg, 0.16 mmol), and dioxane (approximately 62 mL). A second stock solution was prepared consisting of potassium carbonate (1.245 g, 9 mmol) and water (approximately 6.2 mL). The solutions were sonicated and degassed by bubbling nitrogen gas through them. 4 mL of the first stock solution and 0.4 mL of the second stock solution were added to a reaction vial containing (3-aminocarbonylphenyl)boronic acid (available from Apollo Scientific Ltd., Stockport, UK; 99 mg, 0.6 mmol). The mixture was heated in a microwave oven at 170 degrees for 25 min and then passed through a silica gel column (1 g of silica), and washed with dioxane (1 mL) and dimethylacetamide (1 mL). 2 M potassium hydroxide solution (0.4 mL) was added. The mixture was stirred at room temperature overnight, and then 1 M HCl (0.8 mL) was added and the solvents were removed in the Genevac. Aqueous methanol (50%; approximately 2 mL) was added, then the vial was centrifuged and the solvent was removed. This process was repeated to give 3-(3′-carbamoyl-biphenyl-4-yloxymethyl)-benzoic acid. Mass spectrum MH+=348.

Workup

  1. customA first stock solution was prepared
  2. customA second stock solution was prepared
  3. customThe solutions were sonicated
  4. customdegassed
  5. customby bubbling nitrogen gas through them
  6. addition4 mL of the first stock solution and 0.4 mL of the second stock solution were added to a reaction
  7. temperatureThe mixture was heated in a microwave oven at 170 degrees for 25 min
  8. washwashed with dioxane (1 mL) and dimethylacetamide (1 mL)
  9. addition2 M potassium hydroxide solution (0.4 mL) was added
  10. addition1 M HCl (0.8 mL) was added
  11. customthe solvents were removed in the Genevac
  12. additionAqueous methanol (50%; approximately 2 mL) was added
  13. customthe solvent was removed

Sources & evidence

ORD record
ord-de7d22e196674e629e23bd925c175d21
Source dataset
uspto-grants-2009_04
Patent number
US07524870B2

Reaction notes

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