Hydrochloric Acid → 2-(4'-Isopropylcarbamoyl-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

HRID 1801241Notes

Reaction equation

HRID 1801241 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:17]=[C:18]([C:22]3[CH:27]=[CH:26][C:25]([C:28](=[O:33])[NH:29][CH:30]([CH3:32])[CH3:31])=[CH:24][CH:23]=3)[CH:19]=[CH:20][CH:21]=1)[C:10]([CH3:35])([CH3:34])[CH2:9]2)=[O:5])C.[OH-].[Na+].Cl>CO.O1CCCC1.O>[CH:30]([NH:29][C:28]([C:25]1[CH:24]=[CH:23][C:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([CH:11]3[C:10]([CH3:34])([CH3:35])[CH2:9][C:8]4[C:13](=[CH:14][CH:15]=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=4)[NH:12]3)[CH:17]=2)=[CH:27][CH:26]=1)=[O:33])([CH3:32])[CH3:31]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 674428522-(4'-Isopropylcarbamoyl-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester

Product 1

HCID 584761632-(4'-Isopropylcarbamoyl-biphenyl-3-yl)-3,3-dimethyl-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 2-(4′-isopropylcarbamoyl-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (940 mg, 2 mmol) in methanol (15.0 mL) and tetrahydrofuran (16.0 mL) was added 50% sodium hydroxide in water (2.0 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 2-(4′-isopropylcarbamoyl-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (795 mg, 90%) as a white solid: LC/MS m/e calcd for C28H30N2O3 (M+H)+: 443.56, observed: 443.1.

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-b9c46332ab1042d08237962b776708ce
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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