Morpholine → 8-Quinolinecarboxylic acid, 6-fluoro-1,2,3,4-tetrahydro-4,4-dimethyl-2-[3-(4-morpholinyl)phenyl]-

HRID 2408084Notes

Reaction equation

HRID 2408084 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]([F:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1)[CH2:11][C:10]2([CH3:23])[CH3:22])=[O:4].[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[F:24][C:7]1[CH:8]=[C:9]2[C:14](=[C:5]([C:3]([OH:2])=[O:4])[CH:6]=1)[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:16]=1)[CH2:11][C:10]2([CH3:23])[CH3:22]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 70496195HCID 70496195, compound

Product 1

HCID 704974208-Quinolinecarboxylic acid, 6-fluoro-1,2,3,4-tetrahydro-4,4-dimethyl-2-[3-(4-morpholinyl)phenyl]-Yield 61.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture solution of 2-(3-bromo-phenyl)-6-fluoro-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (5 g, 12.7 mmol), morpholine (11.1 mL, 125 mmol), copper(I) iodide (1.43 g, 7.5 mmol), N,N-dimethylglycine hydrochloride (1.4 g, 10 mmol), and potassium carbonate (5.2 g, 75 mmol) in dimethyl sulfoxide (20 mL) was stirred at 120° C. for 16 h. Then the reaction mixture was cooled to room temperature. The reaction mixture was extracted with ethyl acetate (150 mL×2), washed with saturated aqueous ammonium chloride solution (50 mL×3) and brine (50 mL×2), dried over anhydrous sodium sulfate and then concentrated in vacuo and the residue was purified by ISCO combi-flash chromatography (gradient elution, 30-50% ethyl acetate in petroleum ether) to afford 6-fluoro-4,4-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid (3 g, 61%) as a white solid: MS (ESI) M+1=385.1.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (150 mL×2)
  2. washwashed with saturated aqueous ammonium chloride solution (50 mL×3) and brine (50 mL×2)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customthe residue was purified by ISCO combi-flash chromatography (gradient elution, 30-50% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-6280aa0660a24076aa727036e2d482b0
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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