Morpholine → HCID 66587793, compound

HRID 2407965Notes

Reaction equation

HRID 2407965 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1)[CH2:9][C:8]2([CH3:23])[CH3:22])=[O:4].[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:16]=1)[CH2:9][C:8]2([CH3:23])[CH3:22])=[O:4]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 66587676HCID 66587676, compound

Product 1

HCID 66587793HCID 66587793, compoundYield 80%

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)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (11.2 g, 30.0 mmol), morpholine (26.0 mL, 294.0 mmol), copper(I) iodide (3.4 g, 18.0 mmol), N,N-dimethylglycine hydrochloride (3.4 g, 24.0 mmol), and potassium carbonate (12.4 g, 90.0 mmol) in dimethyl sulfoxide (65 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 (200 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 4,4-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (9.1 g, 80%) as a white solid: MS (ESI) M+1=381.0.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (200 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-275a59448e4a49b2a8f436b4ff939d45
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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