Hydrochloric Acid → 8-Chloro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

HRID 1801141Notes

Reaction equation

HRID 1801141 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([Cl:15])[CH:14]=1)[NH:11][CH:10]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:17]=1)[C:9]([CH3:29])([CH3:28])[CH2:8]2)=[O:4].[OH-].[Na+].Cl>CO.O1CCCC1.O>[Cl:15][C:13]1[CH:14]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=[C:7]2[C:12]=1[NH:11][CH:10]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[CH:17]=1)[C:9]([CH3:28])([CH3:29])[CH2:8]2

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 674425978-Chloro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester

Product 1

HCID 584762078-Chloro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acidYield 90%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred mixture solution of 8-chloro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (700 mg, 1.8 mmol) in methanol (5.0 mL) and tetrahydrofuran (5.0 mL) was added 50% sodium hydroxide in water (1.0 mL). The reaction mixture was stirred at 70° C. for 6 hours. The mixture was neutralized with a 3 N aqueous hydrochloric acid solution and extracted with ethyl acetate (2×100 mL), washed with water, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 8-chloro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (630 mg, 90%) as a light yellow solid: LC/MS m/e calcd for C22H25ClN2O3 (M+H)+: 401.91, observed: 401.1.

Workup

  1. extractionextracted with ethyl acetate (2×100 mL)
  2. washwashed with water
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water)

Sources & evidence

ORD record
ord-da56585bc8064801a9182f61c34398e6
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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