Potassium Iodide → 3-Methoxy-4-[3-(1-pyrrolidinyl)propoxy]-benzoic acid Hydrochloride

HRID 454005

Reaction equation

HRID 454005 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].[N:13]1([CH2:18][CH2:19][CH2:20][Cl:21])[CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C>[ClH:21].[CH3:12][O:11][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=1[O:1][CH2:20][CH2:19][CH2:18][N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)[C:6]([OH:8])=[O:7]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 8468Vanillic AcidHCID 11430Potassium CarbonateHCID 113210281-(3-Chloropropyl)-pyrrolidine

Product 1

HCID 248202363-Methoxy-4-[3-(1-pyrrolidinyl)propoxy]-benzoic acid HydrochlorideYield 77.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-hydroxy-3-methoxybenzoic acid (8.4 g, 50 mmol), 3-(pyrrolidin-1-yl)propyl chloride (14.75 g, 0.1 mol), (J. Am. Chem. Soc. 1955, 77, 2272), potassium carbonate (13.8 g, 0.1 mol) and potassium iodide (1.66 g, 10 mmol) in DMF (150 ml) was stirred and heated at 100° C. for 3 hours. The mixture was allowed to cool and the insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was dissolved in ethanol (75 ml), 2M aqueous sodium hydroxide (75 ml) was added and the mixture was heated at 90° C. for 2 hours. The mixture was concentrated by evaporation, 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 dilute hydrochloric acid (pH2.2). The methanol was removed by evaporation and the aqueous residue was freeze dried to give 3-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzoic acid hydrochloride (12.2 g, 77%).

Workup

  1. temperatureto cool
  2. customthe insolubles were removed by filtration
  3. customthe volatiles were removed from the filtrate by evaporation
  4. dissolutionThe residue was dissolved in ethanol (75 ml)
  5. addition2M aqueous sodium hydroxide (75 ml) was added
  6. temperaturethe mixture was heated at 90° C. for 2 hours
  7. concentrationThe mixture was concentrated by evaporation
  8. washwashed with ether
  9. customsubjected to purification on a Diaion (trade mark of Mitsubishi) HP20SS resin column
  10. washeluting with water
  11. customThe methanol was removed by evaporation
  12. customdried

Sources & evidence

ORD record
ord-62999f3dce0d4398a39d059cd2a0c7f4
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Linked notes

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