Hydrochloric Acid → 6-Quinolinecarboxylic acid, 2-[4-fluoro-3-(4-morpholinyl)phenyl]-1,2,3,4-tetrahydro-3,3-dimethyl-

HRID 1801009Notes

Reaction equation

HRID 1801009 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]([C:16]1[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:19]([F:28])=[CH:18][CH:17]=1)[C:10]([CH3:30])([CH3:29])[CH2:9]2)=[O:5])C.O.[OH-].[Li+].O.Cl>O1CCCC1>[F:28][C:19]1[CH:18]=[CH:17][C:16]([CH:11]2[C:10]([CH3:29])([CH3:30])[CH2:9][C:8]3[C:13](=[CH:14][CH:15]=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=3)[NH:12]2)=[CH:21][C:20]=1[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 67439972HCID 67439972, compound

Product 1

HCID 674410266-Quinolinecarboxylic acid, 2-[4-fluoro-3-(4-morpholinyl)phenyl]-1,2,3,4-tetrahydro-3,3-dimethyl-Yield 57.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-(4-fluoro-5-morpholin-4-yl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.11 g, 0.27 mmol), lithium hydroxide hydrate (0.11 g, 2.7 mmol), water (2 mL) in tetrahydrofuran (10 mL) was stirred at 60° C. for 12 h. The mixture was neutralized with a 3 N aqueous hydrochloric acid solution and extracted with ethyl acetate (2×50 mL), washed with water, dried over anhydrous sodium sulfate and then concentrated in vacuo to afford an oil residue. 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% formic acid in water) afforded 2-(4-fluoro-3-morpholin-4-yl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (60 mg, 57%) as a white solid: LC/MS m/e calcd for C22H25FN2O3 (M+H)+: 385.5, observed: 385.3.

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washwashed with water
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto afford an oil residue
  6. 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% formic acid in water)

Sources & evidence

ORD record
ord-45b3ced89f45493bb06b9ff3f8d88ee1
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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