Sodium Hydroxide → 4-Amino-5-(cyclopentylmethoxy)-2-methylquinoline-3-carboxylic acid

HRID 2047739Notes

Reaction equation

HRID 2047739 reaction equation
C([O:3][C:4]([C:6]1[C:7]([CH3:24])=[N:8][C:9]2[C:14]([C:15]=1[NH2:16])=[C:13]([O:17][CH2:18][CH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1)[CH:12]=[CH:11][CH:10]=2)=[O:5])C.[OH-].[Na+]>CCO>[NH2:16][C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][C:13]=2[O:17][CH2:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[N:8]=[C:7]([CH3:24])[C:6]=1[C:4]([OH:5])=[O:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66745974Ethyl 4-amino-5-(cyclopentylmethoxy)-2-methylquinoline-3-carboxylate

Product 1

HCID 545884934-Amino-5-(cyclopentylmethoxy)-2-methylquinoline-3-carboxylic acidYield 49%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl-4-amino-5-(cyclopentylmethoxy)-2-methylquinoline-3-carboxylate (Example 18a, 16.8 g, 51.2 mmol) in EtOH (100 mL) was added NaOH (2 N, 64 mL) at room temperature. The reaction mixture was refluxed for 4 h. After it was cooled down to room temperature, the reaction solution was filtered to remove any possible solid residue. The filtrate was carefully neutralized with 2N HCl to pH 7 at 0° C. The resultant precipitate was collected by filtration, washed with water, re-dissolved in EtOH (500 mL) and water (30 mL), and treated with activated charcoal (650 mg) at 70° C. for 0.5 h. The charcoal was removed by filtration, and the filtrate was concentrated and stored at 4° C. overnight. The resulting precipitate was collected by filtration, washed with cold 25% EtOH in H2O, and dried under vacuum at 60° C. overnight to give the title compound as an off-white solid (7.5 g, 49%). 1H NMR (400 MHz, DMSO-d6) δ 1.31-1.37 (m, 2H), 1.53-1.64 (m, 4H), 1.79-1.85 (m, 2H), 2.47-2.50 (m, 1H), 2.75 (s, 3H), 4.11 (d, J=8.8 Hz, 2H), 7.03 (d, J=8.0 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 7.66 (t, J=8.0 Hz, 1H), 8.77 (brs, 1H), 12.26 (brs, 1H), 12.75 (brs, 1H). 1H NMR (400 MHz, CD3OD) δ 1.39-1.49 (m, 2H), 1.63-1.77 (m, 4H), 1.91-1.98 (m, 2H), 2.51-2.61 (m, 1H), 2.78 (s, 3H), 4.16 (d, J=8.0 Hz, 2H), 7.08 (d, J=8.0 Hz, 1H), 7.23 (d, J=8.0 Hz, 1H), 7.72 (t, J=8.0 Hz, 1H). MS 301 (MH+).

Workup

  1. temperatureThe reaction mixture was refluxed for 4 h
  2. filtrationthe reaction solution was filtered
  3. customto remove any possible solid residue
  4. customwas carefully neutralized with 2N HCl to pH 7 at 0° C
  5. filtrationThe resultant precipitate was collected by filtration
  6. washwashed with water
  7. dissolutionre-dissolved in EtOH (500 mL)
  8. additionwater (30 mL), and treated with activated charcoal (650 mg) at 70° C. for 0.5 h
  9. customThe charcoal was removed by filtration
  10. concentrationthe filtrate was concentrated
  11. filtrationThe resulting precipitate was collected by filtration
  12. washwashed with cold 25% EtOH in H2O
  13. customdried under vacuum at 60° C. overnight

Sources & evidence

ORD record
ord-769313a1f28e44a29367c4f03d99ae26
Source dataset
uspto-grants-2013_11
Patent number
US08592592B2

Reaction notes

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