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

HRID 1741042Notes

Reaction equation

HRID 1741042 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][C:3]=1[CH3:10].B([C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=1)(O)O.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:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=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-boronobenzoic 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 tetrakis (triphenylphosphine)palladium (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 washed 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 filtered through kieselguhr to give a pale yellow solution, which was acidified to pH 5 using conc. HCl to give an off white precipitate. This was filtered off, washed with water and dried in vacuo to give the title compound as on off white solid (5.85 g, 56%).

Workup

  1. customThe reaction mixture was then flushed with argon and tetrakis (triphenylphosphine)palladium (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. washwashed with EtOAc (2×150 ml)
  9. stirringstirred for 1 h at room temperature
  10. filtrationThe resulting pale brown solution was filtered through kieselguhr
  11. customto give a pale yellow solution, which
  12. customto give an off white precipitate
  13. filtrationThis was filtered off
  14. washwashed with water
  15. customdried in vacuo

Sources & evidence

ORD record
ord-c814e05697824393b23fcf3b33468e6f
Source dataset
uspto-grants-1999_10
Patent number
US05972951

Reaction notes

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