Morpholine → HCID 67439972, compound

HRID 1801008Notes

Reaction equation

HRID 1801008 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18](Br)[CH:17]=1)[C:10]([CH3:25])([CH3:24])[CH2:9]2)=[O:5])[CH3:2].[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]([C:16]1[CH:17]=[C:18]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[C:19]([F:22])=[CH:20][CH:21]=1)[C:10]([CH3:25])([CH3:24])[CH2:9]2)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 67441427HCID 67441427, compound

Product 1

HCID 67439972HCID 67439972, compoundYield 17.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-(3-bromo-4-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.63 g, 1.55 mmol), morpholine (1.35 g, 15.5 mmol), copper (I) iodide (0.18 g, 0.93 mmol), L-proline (89 mg, 0.78 mmol) and potassium carbonate (0.64, 4.65 mmol) in DMSO (3 mL) was heated for 4 hours at 120° C. After cooling to room temperature, the mixture was treated with ethyl acetate (50 mL) and washed with water (20 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. Purification on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (20% ethyl acetate/hexanes) to afford 2-(4-fluoro-5-morpholin-4-yl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.11 g, 17%) as a white solid: LC/MS m/e calcd for C24H29FN2O3 (M+H)+: 413.5, observed: 413.4.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (20 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f201c9ddcc2f4d75bc0cedf9a5d6b112
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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