Hydrochloric Acid → 5-Chloro-N-methyl-N-propyl-isophthalamic acid

HRID 732503Notes

Reaction equation

HRID 732503 reaction equation
CO[C:3](=[O:15])[C:4]1[CH:13]=[C:12]([Cl:14])[CH:11]=[C:6]([C:7]([O:9]C)=[O:8])[CH:5]=1.[OH-].[Na+].COC(=O)C1C=C(Cl)C=C(C(O)=O)C=1.Cl.[CH3:33][N:34](C)[CH2:35][CH2:36][CH2:37]N=C=NCC.ON1C2C=CC=CC=2N=N1.CNCCC.[OH-].[Li+].Cl>CC(C)=O.CO.CN(C=O)C.C(OCC)(=O)C>[Cl:14][C:12]1[CH:13]=[C:4]([C:3]([N:34]([CH3:33])[CH2:35][CH2:36][CH3:37])=[O:15])[CH:5]=[C:6]([CH:11]=1)[C:7]([OH:9])=[O:8]

Participants

13

Reactant 8

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 12315N-MethylpropylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 224975Dimethyl 5-chloroisophthalateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 247289213-Chloro-5-(methoxycarbonyl)benzoic acid

Product 1

HCID 688147425-Chloro-N-methyl-N-propyl-isophthalamic acid

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve commercially available 5-chloroisophthalic acid dimethyl ester (1.0 g, 4.37 mmol) in acetone (10 mL) and add a solution of NaOH (192 mg, 4.81 mmol) in methanol (2 mL). Stir 3 h and concentrate. Partition the residue between diethyl ether and water. Acidify the water layer to about pH=1 and collect the precipitate, 5-chloro-isophthalic acid monomethyl ester (675 mg, 72%). Dissolve 5-chloro-isophthalic acid monomethyl ester (459 mg, 2.13 mmol) in DMF (20 mL), add 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (513 mg, 2.67 mmol) and 1-hydroxybenzotriazole (360 mg, 2.67 mmol). Stir at room temperature 1 h and add methyl propylamine (584 mg, 8.0 mmol). Stir at room temperature 3 h, dilute with ethyl acetate, wash with 10% aqueous potassium carbonate, 0.1 N citric acid, 1 N lithium chloride and saturated aqueous sodium chloride and concentrate. Dissolve the residue in THF (30 mL) and add 1 N lithium hydroxide (10 mL, 10 mmol). Stir at room temperature 3 h and acidify to about pH=1 by addition of 1 N HCl. Extract with diethyl ether, dry (magnesium sulfate) and concentrate to give the title compound.

Workup

  1. concentrationconcentrate
  2. customPartition the residue between diethyl ether and water
  3. customcollect the precipitate, 5-chloro-isophthalic acid monomethyl ester (675 mg, 72%)
  4. stirringStir at room temperature 1 h
  5. stirringStir at room temperature 3 h
  6. washwash with 10% aqueous potassium carbonate, 0.1 N citric acid, 1 N lithium chloride and saturated aqueous sodium chloride
  7. concentrationconcentrate
  8. dissolutionDissolve the residue in THF (30 mL)
  9. stirringStir at room temperature 3 h
  10. extractionExtract with diethyl ether
  11. dry with materialdry (magnesium sulfate)
  12. concentrationconcentrate

Sources & evidence

ORD record
ord-63240fe1c894484484332d474848f5a6
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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