Morpholine → HCID 70497656, compound

HRID 2408009Notes

Reaction equation

HRID 2408009 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]=[C:19](Br)[CH:18]=[CH:17][C:16]=1[CH3:22])[CH2:9][C:8]2([CH3:24])[CH3:23])=[O:4].[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.Cl.[CH3:32]N(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH2:1]([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]=[C:19]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:18]=[CH:17][C:16]=1[CH3:22])[CH2:9][C:8]2([CH3:24])[CH3:23])=[O:4])[CH3:32]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 70496690HCID 70496690, compound

Product 1

HCID 70497656HCID 70497656, compoundYield 112.5%

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-(5-bromo-2-methyl-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (3.5 g, 8.7 mmol), morpholine (7.6 mL, 87 mmol), copper(I) iodide (1 g, 5.22 mmol), N,N-dimethylglycine hydrochloride (0.97 g, 6.96 mmol), and potassium carbonate (3.6 g, 26.1 mmol) in dimethyl sulfoxide (25 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-(2-methyl-5-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (3.2 g, 90%) as a white solid: MS (ESI) M+1=409.0.

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-a7d45b8784f84eebad3bd4ab82eb68f1
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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