Hydrochloric Acid → 2-(3-Bromophenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylic acid

HRID 2045443Notes

Reaction equation

HRID 2045443 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]=[CH:20][CH:19]=[C:18]([Br:22])[CH:17]=1)[C:10]([CH3:24])([CH3:23])[CH2:9]2)=[O:5])C.[OH-].[Na+].Cl>CO.O1CCCC1.O>[Br:22][C:18]1[CH:17]=[C:16]([CH:11]2[C:10]([CH3:23])([CH3:24])[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]=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 674428312-(3-Bromo-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester

Product 1

HCID 584761942-(3-Bromophenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylic acidYield 90%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred mixture solution of 2-(3-bromo-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (15 g, 38.7 mmol) in methanol (50.0 mL) and tetrahydrofuran (50.0 mL) was added 50% sodium hydroxide in water (8.0 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 to afford 2-(3-bromo-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (12.5 g, 90%) as a light yellow solid: LC/MS m/e calcd for C15H15BrNO2 (M+H)+: 361.25, observed: 360.0 & 362.0. A mixture of 2-(3-bromo-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (600 mg, 1.7 mmol), (R)-4-isopropyl-2-oxazolidinone (322 mg, 2.5 mmol), copper(I) iodide (96 mg, 0.5 mmol), N,N-dimethylglycine hydrochloride (140 mg, 1.0 mmol) and potassium carbonate (923 mg, 6.7 mmol) in dimethyl sulfoxide (5 mL) was stirred at 120° C. for 16 h. Then the reaction mixture cooled to room temperature. The reaction mixture was extracted with ethyl acetate (2×150 mL), washed with water (2×50 mL) and saturated aqueous ammonium chloride solution (2×50 mL), 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 2-[3-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (555 mg, 80%) as a white solid: LC/MS m/e calcd for C24H28N2O4 (M+H)+: 409.50, observed: 409.1.

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

Sources & evidence

ORD record
ord-9e23627db9c74003bddb28b4b28aacfd
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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