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

HRID 1427105Notes

Reaction equation

HRID 1427105 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.C(Cl)(=O)C(Cl)=[O:14].[NH2:18][C:19]1[C:29](C)=[CH:28]C(C(OCC)=O)=[CH:21][C:20]=1[CH3:31].N1C=CC=CC=1.[CH2:38]1[CH2:42][O:41][CH2:40][CH2:39]1>C(Cl)Cl.CN(C)C1C=CN=CC=1.CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([NH:18][C:19]1[C:29]([CH3:28])=[C:38]([CH:39]=[CH:21][C:20]=1[CH3:31])[C:42]([O:41][CH3:40])=[O:14])=[O:9]

Participants

9

Reactant 5

HCID 1049PyridineHCID 8028TetrahydrofuranHCID 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 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

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 μmoles) 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-7828f7d23b1e46e0a7f776d0b69364a2
Source dataset
uspto-grants-2015_01
Patent number
US08933098B2

Reaction notes

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