Morpholine → HCID 70497766, compound

HRID 2408103Notes

Reaction equation

HRID 2408103 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([CH3:15])[CH:14]=1)[NH:11][CH:10]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18](Br)[CH:17]=1)[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.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](=[C:13]([CH3:15])[CH:14]=1)[NH:11][CH:10]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:17]=1)[CH2:9][C:8]2([CH3:24])[CH3:23])=[O:4]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 70496719HCID 70496719, compound

Product 1

HCID 70497766HCID 70497766, compoundYield 98.6%

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)-4,4,8-trimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (1.4 g, 3.6 mmol), morpholine (4.3 mL, 50 mmol), copper(I) iodide (274 mg, 1.44 mmol), N,N-dimethylglycine hydrochloride (0.3 g, 2.16 mmol), and potassium carbonate (1.49 g, 10.8 mmol) in dimethyl sulfoxide (10 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 4,4,8-trimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (1.4 g, 98%) as a white solid: MS (ESI) M+1=394.2.

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-4b854b357b2c42ca98b772758c43a91a
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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