Potassium Iodide → 3-Methoxy-4-(3-morpholinopropoxy)benzoic acid

HRID 1386253Notes

Reaction equation

HRID 1386253 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[O:11][CH3:12].[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21]Cl)[CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C>[CH3:12][O:11][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=1[O:1][CH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)[C:6]([OH:8])=[O:7]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 8468Vanillic AcidHCID 11430Potassium CarbonateHCID 958344-(3-Chloropropyl)morpholine

Product 1

HCID 216992843-Methoxy-4-(3-morpholinopropoxy)benzoic acidYield 109.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-hydroxy-3-methoxybenzoic acid (4.5 g, 26.8 mmol), 3-morpholinopropyl chloride (9.5 g, 58.0 mmol), (prepared according to J. Am. Chem. Soc. 1945, 67, 736), potassium carbonate (8.0 g, 58 mmol), potassium iodide (1.0 g, 0.22 mmol) and DMF (80 ml) was stirred and heated at 100° C. for 3 hours. The solid was removed by filtration and the filtrate evaporated. The residue was dissolved in ethanol (50 ml), 2M sodium hydroxide (50 ml) was added and the mixture heated at 90° C. for 2 hours. After partial evaporation, the mixture was acidified with concentrated hydrochloric acid, washed with ether and then subjected to purification on a Diaion (trade mark of Mitsubishi) HP20SS resin column, eluting with water and then with a gradient of methanol (0 to 25%) in hydrochloric acid (pH2). Partial evaporation of the solvents and lyophilisation gave 3-methoxy-4-(3-morpholinopropoxy)benzoic acid (8.65 g, 97%).

Workup

  1. customThe solid was removed by filtration
  2. customthe filtrate evaporated
  3. dissolutionThe residue was dissolved in ethanol (50 ml)
  4. addition2M sodium hydroxide (50 ml) was added
  5. temperaturethe mixture heated at 90° C. for 2 hours
  6. customAfter partial evaporation
  7. washwashed with ether
  8. customsubjected to purification on a Diaion (trade mark of Mitsubishi) HP20SS resin column
  9. washeluting with water
  10. customPartial evaporation of the solvents and lyophilisation

Sources & evidence

ORD record
ord-12ee9487f4bb491c8c0c121595a05c03
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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