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

HRID 2169849Notes

Reaction equation

HRID 2169849 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[N:5]=[C:4]([CH3:19])[C:3]=1[C:20]([O:22]CC)=[O:21].[OH-].[Na+]>CCO>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[N:5]=[C:4]([CH3:19])[C:3]=1[C:20]([OH:22])=[O:21]

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 NR (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 NR (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-0c4d4d6ae0f2436b9bd1f143c5d81a96
Source dataset
uspto-grants-2015_06
Patent number
US09049878B2

Reaction notes

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