Hydrochloric Acid → 6-Chloro-2-{3-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid

HRID 2045366Notes

Reaction equation

HRID 2045366 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]([Cl:36])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([C:27]4[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=4)[CH2:23][CH2:22]3)[CH:16]=1)[C:11]([CH3:35])([CH3:34])[CH2:10]2)=[O:4].O.[OH-].[Li+].O.Cl>CO.O1CCCC1>[Cl:36][C:7]1[CH:8]=[C:9]2[C:14](=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=1)[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:22][CH2:23][N:24]([C:27]4[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][CH:32]=4)[CH2:25][CH2:26]3)[CH:16]=1)[C:11]([CH3:35])([CH3:34])[CH2:10]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 674426056-Chloro-2-{3-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

Product 1

HCID 674411956-Chloro-2-{3-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acidYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 6-chloro-2-{3-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (0.13 g, 0.25 mmol), lithium hydroxide hydrate (104 mg, 2.5 mmol), water (0.5 mL) in methanol (1 mL) and tetrahydrofuran (5 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 6-chloro-2-{3-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid (100 mg, 80%) as a white solid: LC/MS m/e calcd for C28H29Cl2N3O2 M+: 510.5, observed: 510.0;

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-8ebb8d21ef48477bb1379c96ee25d1bc
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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