Hydrochloric Acid → 4'-Acetamidomethyl-2'-methylbiphenyl-4-carboxylic acid

HRID 399261Notes

Reaction equation

HRID 399261 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][C:3]=1[CH3:10].[C:11]([C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1)([OH:13])=[O:12].C(=O)([O-])[O-].[Na+].[Na+].[C:29](OC(=O)C)(=[O:31])[CH3:30].Cl>COCCOC.O>[C:29]([NH:7][CH2:6][C:5]1[CH:8]=[CH:9][C:2]([C:17]2[CH:18]=[CH:19][C:14]([C:11]([OH:13])=[O:12])=[CH:15][CH:16]=2)=[C:3]([CH3:10])[CH:4]=1)(=[O:31])[CH3:30]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 21756143(4-Bromo-3-methylphenyl)methanamine

Product 1

HCID 218338034'-Acetamidomethyl-2'-methylbiphenyl-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

4-Bromo-3-methylbenzylamine (EP 532266) (7.36 g, 0.037 mol) was dissolved in 1,2-dimethoxyethane (DME) (180 ml), with stirring, and was treated with 4-carboxyphenyl boronic acid (6.14 g, 0.037 mol), followed by a solution of sodium carbonate (17.65 g, 0.167 mol) in water (180 ml). The reaction mixture was then flushed with argon and tetrakistriphenylphosphinepalladium (O) (1.00 g) was added. The reaction mixture was then heated to reflux under argon. After 16 h, the reaction mixture was allowed to cool and the DME was removed by evaporation under reduced pressure. The aqueous residue was then diluted with water (~200 ml) and extracted with EtOAc (2×150 ml). The aqueous layer was then treated with acetic anhydride (6.98 ml, 0.074 mol) and stirred for 1 h at room temperature. The resulting pale brown solution was then filtered through kieselguhr to give a pale yellow solution which was acidified to pH5 using conc. HCl to give an off white precipitate which was filtered off, washed with water and dried in vacuo to give the title compound as an off white solid (5.85 g, 56%).

Workup

  1. customThe reaction mixture was then flushed with argon and tetrakistriphenylphosphinepalladium (O) (1.00 g)
  2. additionwas added
  3. temperatureThe reaction mixture was then heated
  4. temperatureto reflux under argon
  5. temperatureto cool
  6. customthe DME was removed by evaporation under reduced pressure
  7. additionThe aqueous residue was then diluted with water (~200 ml)
  8. extractionextracted with EtOAc (2×150 ml)
  9. stirringstirred for 1 h at room temperature
  10. filtrationThe resulting pale brown solution was then filtered through kieselguhr
  11. customto give a pale yellow solution which
  12. customto give an off white precipitate which
  13. filtrationwas filtered off
  14. washwashed with water
  15. customdried in vacuo

Sources & evidence

ORD record
ord-3a629c8dc94d47b3b9e55db507b2abc8
Source dataset
uspto-grants-1998_10
Patent number
US05817833

Reaction notes

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