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

HRID 239951Notes

Reaction equation

HRID 239951 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=1)C(O)=O.[CH3:12][N:13]([CH:15]=[O:16])C.[C:17](Cl)(=O)C(Cl)=O.NC1[C:34]([CH3:35])=[CH:33][C:27]([C:28]([O:30][CH2:31]C)=[O:29])=[CH:26][C:25]=1C.N1C=CC=CC=1>C1COCC1.C(Cl)Cl.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:10]=[CH:6][C:5]([CH3:11])=[C:4]([CH:3]=1)[C:15]([NH:13][C:12]1[C:26]([CH3:25])=[C:27]([CH:33]=[CH:34][C:35]=1[CH3:17])[C:28]([O:30][CH3:31])=[O:29])=[O:16]

Participants

9

Reactant 5

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

Product 1

HCID 86707319Methyl 3-[(5-bromo-2-methyl-benzoyl)amino]-2,4-dimethyl-benzoateYield 95.5%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-bromo-2-methyl-benzoic acid (2.45 g, 11.16 mmol) in THF (10 ml), CH2Cl2 (10 ml) and DMF (20.00 μl, 258.65 moles) is added dropwise oxalyl chloride (1.16 ml, 13.39 mmoles) at 0° C. and the reaction mixture is slowly allowed to warm to ambient temperature. After 2 hours, the solvent is removed under reduced pressure. To the residue is added CH2Cl2 (40 ml) and the reaction mixture is cooled to 0° C., then ethyl 4-amino-3,5-dimethyl-benzoate (2 g, 11.16 mmol) is added followed by N,N-dimethylpyridin-4-amine (13.63 mg, 0.11 mmoles) and pyridine (2.71 ml, 33.48 mmoles). The cooling bath is removed and the clear solution is allowed to warm to ambient temperature. After 2 hours, the solvent is removed and the reaction mixture is diluted with ethyl acetate and washed with 1N HCl, a saturated solution of sodium bicarbonate, and brine. The organic layers are combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the title compound as a light yellow solid (4.0 g; 95.5%). Mass spectrum (m/z): 376.0 (M+1).

Workup

  1. customthe solvent is removed under reduced pressure
  2. additionTo the residue is added CH2Cl2 (40 ml)
  3. temperaturethe reaction mixture is cooled to 0° C.
  4. customThe cooling bath is removed
  5. temperatureto warm to ambient temperature
  6. waitAfter 2 hours
  7. customthe solvent is removed
  8. additionthe reaction mixture is diluted with ethyl acetate
  9. washwashed with 1N HCl
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-385f756762524a5f93b9fec4e245e669
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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