Sodium Hydroxide → 4-[3-Methyl-1-(8-methyl-quinolin-3-ylamino)-butyl]benzoic acid

HRID 2281146Notes

Reaction equation

HRID 2281146 reaction equation
C([O:3][C:4](=[O:28])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([NH:16][C:17]2[CH:18]=[N:19][C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:27])[CH2:12][CH:13]([CH3:15])[CH3:14])=[CH:7][CH:6]=1)C.[OH-].[Na+]>C1COCC1.CO>[CH3:14][CH:13]([CH3:15])[CH2:12][CH:11]([C:8]1[CH:7]=[CH:6][C:5]([C:4]([OH:28])=[O:3])=[CH:10][CH:9]=1)[NH:16][C:17]1[CH:18]=[N:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:27]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 712395254-[3-Methyl-1-(8-methyl-quinoline-3-ylamino)-butyl]-benzoic acid ethyl ester

Product 1

HCID 712394574-[3-Methyl-1-(8-methyl-quinolin-3-ylamino)-butyl]benzoic acidYield 79.6%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4-[3-Methyl-1-(8-methyl-quinoline-3-ylamino)-butyl]-benzoic acid ethyl ester (62 mg, 0.16 mM) and 1N aqueous NaOH solution (0.413 mL, 0.413 mM) in THF-MeOH (1:1, 3.3 mL) was heated to 50° C. for 4 h. The reaction was cooled, concentrated to remove organic solvent. The aqueous solution was diluted with DCM (5 mL), acidified by 1N HCl solution to pH=3-4. The organic solution was separated and the aqueous solution was extracted with 10% i-PrOH-DCM (5×5 mL). The combined organic solution were dried (Na2SO4) and concentrated to give a yellow solid product (45.7 mg, 79%). 1H NMR (400 MHz, CD3OD) δ ppm 0.98 (d, J=6.44 Hz, 3 H) 1.03 (d, J=6.25 Hz, 3 H) 1.56-1.68 (m, 1 H) 1.73-1.93 (m, 2 H) 2.68 (d, 3 H) 4.60-4.68 (m, 1 H) 7.23-7.35 (m, 2 H) 7.38 (d, 1 H) 7.44 (d, 1 H) 7.48-7.61 (m, 2 H) 7.96 (d, 2 H) 8.53 (dd, 1 H), two protons (COOH and NH) were exchanged. This material will be used for the next step reaction without further work-up.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated
  3. customto remove organic solvent
  4. additionThe aqueous solution was diluted with DCM (5 mL)
  5. customThe organic solution was separated
  6. extractionthe aqueous solution was extracted with 10% i-PrOH-DCM (5×5 mL)
  7. dry with materialThe combined organic solution were dried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-df846e72e7aa4cd3ae5386f1369f13ec
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

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