Hydrochloric Acid → 2-(5-Fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

HRID 1801015Notes

Reaction equation

HRID 1801015 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]([F:22])[CH:19]=[CH:18][C:17]=1[CH3:23])[C:10]([CH3:25])([CH3:24])[CH2:9]2)=[O:5])C.O.[OH-].[Li+].O.Cl>O1CCCC1>[F:22][C:20]1[CH:19]=[CH:18][C:17]([CH3:23])=[C:16]([CH:11]2[C:10]([CH3:24])([CH3:25])[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]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 674430852-(5-Fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester

Product 1

HCID 674418742-(5-Fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acidYield 40.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-(5-fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.70 g, 2.05 mmol), lithium hydroxide hydrate (0.86 g, 20.5 mmol), water (3 mL) in tetrahydrofuran (30 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-(5-fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (260 mg, 40%) as a white solid: LC/MS m/e calcd for C19H20FNO2 (M+H)+: 314.4, observed: 314.3.

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-5ce831a0b5de4b51bb9b418a456b85d4
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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