Pyridine → Ethyl 4-[(5-bromo-2-methyl-benzoyl)amino]-3,5-dimethyl-benzoate

HRID 239946Notes

Reaction equation

HRID 239946 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:23][C:24]1[C:34]([CH3:35])=[CH:33][C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:26][C:25]=1[CH3:36].N1C=CC(N)=CC=1.N1C=CC=CC=1>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([NH:23][C:24]1[C:25]([CH3:36])=[CH:26][C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:33][C:34]=1[CH3:35])=[O:9]

Participants

9

Reactant 6

HCID 1049PyridineHCID 17274-AminopyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 201013Benzoic acid, 4-amino-3,5-dimethyl-, ethyl esterHCID 3460045-Bromo-2-methylbenzoic acid

Product 1

HCID 86707333Ethyl 4-[(5-bromo-2-methyl-benzoyl)amino]-3,5-dimethyl-benzoateYield 75.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-bromo-2-methyl-benzoic acid (1.35 g, 6.15 mmol) in THF (15 ml), CH2Cl2 (15 ml) and DMF (14.27 μl, 184.57 moles) is added dropwise oxalyl chloride (587.12 μl, 6.77 mmoles) at 0° C. and reaction mixture is slowly allowed to warm to ambient temperature. After 2 hours, the solvent is removed under reduced pressure. To the residue CH2Cl2 (30 ml) is added and reaction mixture is cooled to 0° C., then ethyl 4-amino-3,5-dimethyl-benzoate (1.19 g, 6.15 mmol) is added followed by 4-pyridinamine, N,N-dimethyl-(37.58 mg, 307.61 mmoles) and pyridine (1.49 ml, 18.46 mmoles). The cooling bath is removed and the clear solution is allowed to warm to ambient temperature. After 5 hours, the solvent is removed and the reaction mixture is diluted with ethyl acetate and washed with 1N HCl, saturated solution of sodium bicarbonate, and brine. The organic layers are combined and dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue is triturated with hexanes and the resulting solids were collected by filtration to give the title compound as a white solid (1.80 g; 75.2%). Mass spectrum (m/z): 390.2 (M+1).

Workup

  1. customreaction mixture
  2. customthe solvent is removed under reduced pressure
  3. additionTo the residue CH2Cl2 (30 ml) is added
  4. customreaction mixture
  5. temperatureis cooled to 0° C.
  6. customThe cooling bath is removed
  7. temperatureto warm to ambient temperature
  8. waitAfter 5 hours
  9. customthe solvent is removed
  10. additionthe reaction mixture is diluted with ethyl acetate
  11. washwashed with 1N HCl, saturated solution of sodium bicarbonate, and brine
  12. dry with materialdried over anhydrous Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe resulting residue is triturated with hexanes
  16. filtrationthe resulting solids were collected by filtration

Sources & evidence

ORD record
ord-58dc9aab5fb24b75b92d9a9402670fa5
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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