Morpholine → {1-[4-(8-Morpholin-4-yl-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1037334Notes

Reaction equation

HRID 1037334 reaction equation
[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27](=[O:28])[C:26]4[C:21](=[C:22](Br)[CH:23]=[CH:24][CH:25]=4)[O:20][C:19]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27](=[O:28])[C:26]4[C:21](=[C:22]([N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)[CH:23]=[CH:24][CH:25]=4)[O:20][C:19]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 8083Morpholine3×HCID 10796Cesium carbonate3×HCID 634876Binap, (A+-)-3×HCID 67067700{1-[4-(8-Bromo-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 67067829{1-[4-(8-Morpholin-4-yl-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst3×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

{1-[4-(8-bromo-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (50 mg, 0.091 mmol), morpholine (10 μL, 0.11 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.005 mmol), (S)-BINAP (9 mg, 0.015 mmol) and cesium carbonate (42 mg, 0.127 mmol) were suspended in toluene (1 mL) in a microwave vial. The vial was sealed, evacuated and flushed twice with nitrogen. The reaction mixture was heated in a microwave at 150° C. for 1 h. Further morpholine (10 μL, 0.11 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.005 mmol), (S)-BINAP (9 mg, 0.015 mmol) and cesium carbonate (42 mg, 0.127 mmol) were added to the vial and the resultant mixture was heated in a microwave at 150° C. for 1.5 h. Further morpholine (10 μL, 0.11 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.005 mmol), (S)-BINAP (9 mg, 0.015 mmol) and cesium carbonate (42 mg, 0.127 mmol) were added to the vial and the resultant mixture was heated in a microwave at 150° C. for 1 h. The reaction mixture was diluted with EtOAc, washed with water, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 100% ethyl acetate in DCM) to afford the title compound as a pale yellow solid (35 mg, 70%). LCMS (Method G): RT=4.33 min, [M+H]+=553.

Workup

  1. customThe vial was sealed
  2. customevacuated
  3. customflushed twice with nitrogen
  4. temperaturewas heated in a microwave at 150° C. for 1.5 h
  5. temperaturewas heated in a microwave at 150° C. for 1 h
  6. washwashed with water
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7b5b0da2d9534c34b3852bf023c64732
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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