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

HRID 239923

Reaction equation

HRID 239923 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[NH2:12][C:13]1[C:22]([CH3:23])=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=1[CH3:24].C(N(CC)C(C)C)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:12][C:13]1[C:14]([CH3:24])=[CH:15][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:21][C:22]=1[CH3:23])=[O:9]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 27363155-Bromo-2-fluorobenzoic acidHCID 11030398Benzoic acid, 4-amino-3,5-dimethyl-, methyl ester

Product 1

HCID 86707311Methyl 4-[(5-bromo-2-fluoro-benzoyl)amino]-3,5-dimethyl-benzoateYield 69.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-bromo-2-fluorobenzoic acid (3.50 g, 15.9 mmol) in CH2Cl2 (50 mL) at 0° C. are added methyl 4-amino-3,5-dimethylbenzoate (2.86 g, 15.9 mmol, see preparation 12) and N,N-diisopropylethylamine (8.35 ml, 47.9 mmol). After stirring the reaction mixture for 10 minutes, 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate, 20.5 ml, 31.9 mmol) is added via syringe and stirred at ambient temperature. After 36 hours, the solvent is removed under reduced pressure and the residue is diluted with water and extracted with ethyl acetate. The organic layers are combined and dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) using 10% ethyl acetate in hexane to give the title compound as a white solid (4.20 g, 69%). Mass spectrum (m/z): 380.2 (M+1).

Workup

  1. stirringstirred at ambient temperature
  2. waitAfter 36 hours
  3. customthe solvent is removed under reduced pressure
  4. additionthe residue is diluted with water
  5. extractionextracted with ethyl acetate
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue is purified by flash chromatography (silica gel)

Sources & evidence

ORD record
ord-2081cbea1bf44a5495940329736f8806
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Linked notes

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