Morpholine → HCID 66587793, compound

HRID 2047697Notes

Reaction equation

HRID 2047697 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[CH2:31][CH2:30]C[C@H:25]1[C:26](O)=[O:27].N1CCOCC1>CS(C)=O.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[CH2:25][CH2:26][O:27][CH2:30][CH2:31]3)[CH:16]=1)[CH2:9][C:8]2([CH3:23])[CH3:22])=[O:4]

Participants

7

Reactant 3

HCID 8083MorpholineHCID 145742L-ProlineHCID 66587676HCID 66587676, compound

Product 1

HCID 66587793HCID 66587793, compoundYield 52.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

The mixture of 4,4-dimethyl-2-(3-bromo-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester as prepared according to Example 1 (374 mg, 1 mmol), CuI (60 mg, 0.3 mmol), L-proline (70 mg, 0.6 mmol) and morpholine (440 mg, 5 mmol) in DMSO (5 mL) was stirred at 120° C. for 16 hours under a nitrogen atmosphere. The reaction mixture was diluted with water (20 mL), extracted with ethyl acetate (20 mL×3) and washed with brine (100 mL) and then dried over anhydrous Na2SO4. The solvent was removed in vacuo and the residue was purified by ISCO combi-flash chromatography (gradient elution, 30-60% 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 (200 mg, 52.6%) as a white solid. MS (ESI+) [(M+H)+] 381.1.

Workup

  1. customas prepared
  2. extractionextracted with ethyl acetate (20 mL×3)
  3. washwashed with brine (100 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by ISCO combi-flash chromatography (gradient elution, 30-60% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-1f9b8125dcf547ceabfacb1eb6c80b54
Source dataset
uspto-grants-2013_11
Patent number
US08592594B2

Reaction notes

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