4-Amino-2-chlorobenzonitrile → 5-((3-Chloro-4-cyanophenyl)amino)-2-methyl-5-oxopentanoic acid

HRID 2272618Notes

Reaction equation

HRID 2272618 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][C:5](=[O:8])[O:4][C:3]1=[O:9].[NH2:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[C:13]([Cl:19])[CH:12]=1.ClC1C=C(NC(=O)C(C)CCC(O)=O)C=CC=1C#N>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[Cl:19][C:13]1[CH:12]=[C:11]([NH:10][C:5](=[O:8])[CH2:6][CH2:7][CH:2]([CH3:1])[C:3]([OH:4])=[O:9])[CH:18]=[CH:17][C:14]=1[C:15]#[N:16]

Participants

6

Reactant 3

HCID 887284-Amino-2-chlorobenzonitrileHCID 3015571dihydro-3-methyl-2H-pyran-2,6(3H)-dioneHCID 867297765-((3-Chloro-4-cyanophenyl)amino)-4-methyl-5-oxopentanoic acid

Product 1

HCID 867297755-((3-Chloro-4-cyanophenyl)amino)-2-methyl-5-oxopentanoic acidYield 39.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 3-methyldihydro-2H-pyran-2,6(3H)-dione (876 mg, 6.84 mmol), 4-amino-2-chlorobenzonitrile (1044 mg, 6.84 mmol) and TEA (0.953 mL, 6.84 mmol) in toluene (10 mL) was stirred at 70° C. for 3 hr. To the reaction mixture was added brine at room temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane) to give a mixture (750 mg, 2.67 mmol, 39.1%) of 5-((3-chloro-4-cyanophenyl)amino)-2-methyl-5-oxopentanoic acid and 5-((3-chloro-4-cyanophenyl)amino)-4-methyl-5-oxopentanoic acid, as a colorless powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-58618add03cf49a49c447cb3508cdb67
Source dataset
uspto-grants-2015_09
Patent number
US09120776B2

Reaction notes

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